Brain Cells and Aging

Within the majority of the brain the type of brain cells that send nerve signals generally do not get replaced, however they also generally don’t lose function. Dementia – loss of memory and other cognitive skills – is not a normal part of healthy aging. Age related forgetfulness has to do with loss of the connections between brain cells but the brain cells remain functional – so continuing to take part in learning and social activities may help prevent dementia and forgetfulness by helping to maintain current connections between brain cells and add new connections formed during learning or socializing. 

And yet Alzheimer’s dementia now “afflicts 5% to 10% of the U.S. population over the age of 65 and as much as 45% of the population over 85.” (page 694, Neuroscience, 6th. edition, 1)

Research for medications for Alzheimer’s treatment have focused on reducing the levels of certain types of protein that collect in the damaged areas of the brain of a patient with the condition, however even if successful at reducing the amount of the protein the medications have not been found very helpful for restoring the patient’s cognitive health. (previous post) People with normal brain function also can have excess of the protein and it is also found in the brains of people with autism disorder – confusing, yes. Adequate quality sleep may help the brain waste removal system keep the levels of excess protein from building up to damaging amounts. (previous post on sleep and the glymphatic system) (shorter summary on sleep tips and insomnia: Sleep and Health)

Things that may increase risk include chronic stress and the excess cortisol and inflammatory oxidative stress chemicals production. Moderate exercise may help reduce stress and promote detoxification of inflammatory chemicals. Staying socially and mentally active also may be protective of brain function. Prevention is the best medicine for conditions that cause irreversible degenerative changes such as the damage in Alzheimer’s Disease. Learning about new foods and recipes and then making healthy meals to share with others can be a way to combine physical and mental activity and gain from nutrients that help detoxify inflammatory oxidative stress chemicals. (previous post, Foods for beneficial T-cells) – (Nrf2 promoting foods)

T cells are a type of blood cell with immune system functions. Beneficial T cells can help clear excess protein found in Alzheimer’s (2) while other types can increase inflammation and the types can transform based on the level of oxidative stress chemicals that are present so having antioxidants and other phytonutrients in daily meals can help signal the T-cells to take the beneficial forms instead of the inflammatory forms. (The non euphoria producing endogenous cannabinoid 2-AG (acts at the CB2 receptor, somewhat similar to CBD) may also help signal T cells towards the less inflammatory type, and reduce migration of them. page 96)

Nrf2 is a gene and protein that help promote the more beneficial types of T cells and help the immune system in other ways and also promote our own production of antioxidants for reducing the oxidative stress chemicals that are a natural waste product left from energy metabolism – when blood sugar is turned into a usable form of energy.

The long story is complicated, the short story remains,

  • include moderate exercise most days of the week,
  • have adequate sleep, 6-8 hours/night, ideally with complete darkness, blackout curtains and cover the light from an electric bedside alarm clock (put it in a nearby drawer or cover it with something),
  • get some natural sunshine or full spectrum light during the day if possible (may help with vitamin D, bioactive sulfate, and circadian rhythm metabolism within the body which includes production of melatonin,
  • stay mentally and socially active,
  • reduce stress when possible and/or practice relaxation techniques,
  • drink adequate water and regularly eat a good variety of colorful fresh produce, whole grains, nuts, beans, seeds, and include omega 3 fatty acid sources on a daily or weekly basis.
  • Clean air quality is also important. Formaldehyde (from secondhand smoke or even excessive use of decorative candles), and other air pollutants (released by plastics or new carpeting/flooring for example) can collect in poorly ventilated buildings. See this post for more information about formaldehyde sources and ways to reduce it: Formaldehyde: Health Risks, and Environmental and Dietary Sources.(effectiveselfcare.info)
  • Adequate water, not getting dehydrated regularly, is important enough to repeat because dehydration allows toxins within the body, including formaldehyde, to collect, instead of being removed by the glymphatic/lymphatic and vascular system, and to then be excreted by the kidneys. Brain Formaldehyde is Related to Water Intake Behavior, Ting Li, et al, 2016, (PubMed) A discussion of how much water is typically needed for health each day, and how much protein to eat for basic needs without being too much for long term kidney health, is available in a previous post: Make Every Day Kidney Appreciation Day. (effectiveselfcare.info)

More of the long story – the Cannabinoid Receptor Type 2 is also activated by a phytonutrient called beta-caryophyllene (BCP) which is found in many aromatic herbs and spices including: oregano, cinnamon,  clove , rosemary,  thyme, black pepper, (4), and copaiba oil. (5) Benefits may include reducing inflammation and pain, anti-anxiety, anti-cancer, (4), and protection of the brain by helping reduce increased activity after brain trauma which can lead to scar like tissue walling off the area of trauma instead healing.(5)

The problem in Alzheimer’s may not be the protein itself but instead the cells that over-actively making it in response to inflammatory signals so the solution would be not trying to remove excess protein but to stop the production of excess protein by signaling the overactive cells that all is well again, stop walling off the supposed injury. Formalin, a more dilute buffered form of formaldehyde was the toxin used to create inflammation in an animal based study of the potential benefits of beta-caryophyllene. A dose of 5 mg/Kg purified beta-caryophyllene essential oil given by mouth (rather than by an injection) was found to help reduce inflammatory pain from the formalin. (4) For a 75 kilogram adult that would be a capsule with 375 milligrams of the purified oil.

The herb rosemary is pine needle like plant that has been used as a pain killer in traditional folk medicine for arthritis pain and was thought of a s a memory aid. Studies more recently have found the essential oil beneficial for improving memory. (6)  **Use care when purchasing essential oils, some are intended only for external use either on the skin when diluted in a small amount of milder oil such as almond oil for massage or topical pain relief, or as an aromatic for scent (example, put a few drops on a cotton ball that is attached to a fan or on the outlet of a humidifier to circulate the aroma through a room).

/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.  Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Anna Mietelska-Porowska and Urszula Wojda, “T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer’s Disease: Potential Pools of New Biomarkers,” Journal of Immunology Research, vol. 2017, Article ID 4626540, 17 pages, 2017. https://doi.org/10.1155/2017/4626540. https://www.hindawi.com/journals/jir/2017/4626540/
  3. edited by Karsten Sauer, Klaus Okkenhaug, Lipid Signaling in T Cell Development and Function, Frontiers Media SA, Nov 12, 2015 page 96
  4. A.-L.Klauke, I.Racz, B.Pradier, et al., The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. European Neuropsychopharmacology, Vol. 24, Issue 4, April 2014, Pages 608-620, https://www.sciencedirect.com/science/article/pii/S0924977X13003027
  5. Guimarães-Santos A, Santos DS, Santos IR, et al. Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury. Evidence-based Complementary and Alternative Medicine : eCAM. 2012;2012:918174. doi:10.1155/2012/918174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291111/
  6. Rachel Hosie, Surge in Rosemary Sales as Aromatic Herb Found to Boost Memory, May 19, 2017, independent.co.uk,  https://www.independent.co.uk/life-style/health-and-families/rosemary-sales-surge-herb-boost-memory-holland-barrett-a7745231.html

G3.6.1.8: If magnesium deficiency is cause of a diabetic patient’s pain, why give opioids instead?

Evidence based clinical research from 2009 could have helped save many lives lost to the opioid epidemic if patients were being told and treated with the discovery. (G3.101) Patients with diabetes and chronic pain often don’t experience much if any relief from the use of opioid medications, however that is the standard pain medication that is provided for chronic pain so it is often prescribed to diabetic patients anyway, just a prescription pad after all not a patient (not true). The research study provided magnesium to the diabetic patients as a pretreatment before providing the opioid or along with an IV drip of the medication, and not only was the pain reduced for patients who received magnesium, but the pain level was reduced for several days for the fortunate patients. And some trials of the experimental treatment didn’t provide the opioid medication and yet pain relief was felt by the diabetic patients.

Well that is exciting and it leads me to say – why even bother giving an opioid medication then, if it won’t help to relieve pain that is actually being caused by a magnesium deficiency? Because there is profit to be made by prescribing opioid medications but there isn’t profit to be made writing a magnesium prescription? Pondering is a waste of time for someone in pain.

The research discussion seemed to focus on using 30 mg of magnesium with IVs of morphine or other opioid medication for better pain control, but didn’t address or stress the fact that the 300 mg dose of magnesium had reduced pain levels for patients on its own, without any opioid medication having been given along with the nutrient. Pain control without needing an addictive drug that can cause death if overdosed?

Common sense can be inexpensive – consider the benefits of resolving a problem instead of treating symptoms and ignoring the underlying cause. (Magnesium can also be deadly in overdoses, but that really isn’t as common a cause of death as opioid overdoses.)

  • Read more: Magnesium ions and opioid agonists in vincristine-induced neuropathy, (G3.101).
  • A more recent study found a significant difference between magnesium levels between the patients with diabetes and the control group. Significantly lower levels of magnesium were also noted in association with insulin resistance factors although not with fasting blood sugar levels. Read more: Association of Serum Magnesium Deficiency with Insulin Resistance in Type 2 Diabetes Mellitus, (G3.122)

Trying to replace a natural function with a patented medication is using patient’s pain for the purposes of profit.

Calcium channel blocker medications (PPIs for example) are trying to close the gates and keep the calcium out – and magnesium would be delighted to do that as nature intended if enough of the mineral were being absorbed from the intestines. However many issues with our modern food supply and the contaminants it may contain, may be leading to poor absorption of magnesium and increased loss of magnesium by the kidneys, (too much active hormone D3 can cause increased calcium absorption and loss of magnesium). Note the frequent use of the word “may” – more research is needed, in the meantime an Epsom salt bath or foot soak or use of a topical magnesium chloride product could bypass poor intestinal absorption problems. The magnesium sulfate used in Epsom salt would also provide sulfate which may also be beneficial due to possible contaminants in our modern food supply.

Talking about doing things “traditionally” is nice but our children are not growing up in the same chemical environment that we did, and we didn’t get to experience the food supply that our grandparents enjoyed.

Calcium channel blocker medications make a large profit for the pharmaceutical company – magnesium cannot be patented.

Now that it is clear that emotions and environmental triggers can cause inflammation, which at the same time is a cause of feeling “pain,” it is easy to see why childhood trauma or severe traumatic experiences or ongoing trauma can lead to developing inflammatory conditions such as inflammatory bowel conditions or fibromyalgia and migraine pain. The next section moves into psychological conditions that can be due to emotional trauma but may cause physical symptoms as well as mental symptoms.

See a healthcare provider for medical advice, diagnosis or treatment.

  • Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References:

Only one? – yes, it is an important one:

I found a more recent one that supports the premise that insulin resistance and Type 2 Diabetes may involve an underlying deficiency of magnesium.

G3.6: Antihistamines may help if there is a genetic tendency to overproduce histamine.

Genetic differences in more than 70 genes have been associated with increased itchiness, see summary at the end of this section. (G3.24) Calcium and serotonin levels may be involved in increased itch or arthritis pain signals being sent or perceived. (G3.25) Scratching an itch is considered rude and a chronic itch is often considered funny however it isn’t fun.

Some background information:

Too much or too little calcium and magnesium can affect pain, itching, and mood. The minerals are both electrically active, and provide energy for ion channels which control the transport of messenger chemicals like serotonin across cell membranes – such as nerve cell membranes which might feel like a sensation of itchiness or pain.     

Excess serotonin may be involved, (G3.26, G3.27), and scratching an itch can make the urge to scratch more intense, even worse afterwards, even though there may be a temporary feeling of relief while scratching. (G3.28) Adequate magnesium is essential for reducing pain in arthritis or at least may help reduce pain levels. (G3.27) An antihistamine may help for some types of itching related to genetic conditions. (G3.29)

Excess dopamine levels can also be a cause of an overwhelming urge to scratch – see “grooming behavior” in section 7. When to Report?. The solution there is to figure out why dopamine levels are that elevated. Elevated dopamine can be a symptom of hyperthyroidism but it can also be associated with other conditions.

  • An Itch You Just Can’t Scratch; NIH-funded study identifies proteins that may cause chronic itch. Summary points: The HTR7 gene was found most closely associated with chronic itch in an animal based study, however over 70 genes were found to be more expressed, more active in lab animals with chronic itch. The gene expression of the HTR7 gene was most active in the mice with the worst symptoms of scratching compared to the mice with the least sensitivity. The activity of the TRP1 receptor was also increased in animals with more symptoms. (G.24)
  • Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: in vivo study using TRPA1-deficient mice. Summary points: The TRPA1 receptor is directly activated by calcium levels inside of the cell, and a variety of toxins or “noxious” (irritating) substances that are produced as a normal part of “oxidative stress” otherwise known as “inflammation” including, “4-hydroxy-2-nonenal, hydrogen peroxide, hypochloride, hydrogen sulphide, 15-delta prostaglandin J2 [2528].” and irritants from the environment or diet can also activate the TRPA1 receptor, *1.mustard oil (allyl isothiocyanate: AITC) [29], *2. cinnamaldehyde [30, 31], *3. allicin [32, 33] and *4. formalin [34]…”. (G3.25) Serotonin and other “Inflammatory mediators, such as bradykinin…[19, 35]” (G3.25) can make the receptors more sensitive which can lead to increased responsiveness of nerve endings – more pain (G3.25) or itch. (G3.24) *See the next section for more information about the chemicals in bold font and where they may be found in the diet or environment.

*People with overactive TRPA1 channels may be sensitive to:

  1. Mustard:  “mustard oil”
  2. Cinnamon:  “cinnamaldehyde'” (G3.43) );
  3. Onion or Garlic:allicin,” (G3.41)
  4. Formaldehyde:formalin,” chemically the two are very similar: (G3.42) and formaldehyde is found in the environmental and as a metabolite of some alternative sweeteners and other dietary sources. (G3.56) Environmental sources include which would include first and second hand smoke, poorly ventilated air or smog, especially when there is brand new flooring or other new plastic or vinyl  material in the living area, it  can release volatile chemicals including formaldehyde at levels that can make a sensitive person feel ill. Metabolites of the breakdown of the alternative sweetener aspartame and Neotame include menthol and formaldehyde. (G3.44) Older packages of fruit juice also may contain increasing amounts of formaldehyde as the product ages, more of the chemical is produced from other chemicals.

Magnesium, Opioids, and Neuropathic Pain.

This list and this section got much longer actually, and eventually led me back to a topic I’ve written about in 2011, and which is one of the underlying causes of overactive TRP channels. Fortunately it also has a simple solution, (G3.101), but – unfortunately – it is so simple a solution that it isn’t profitable – unfortunately for individual patient’s health and quality of life and unfortunately for the economic health of individuals and nations and businesses who are being overcharged by the medical industry for healthcare that isn’t always effective and sometimes causes harm.

It is so effective a solution for improving mood and pain and muscle cramp type symptoms that I’ve been sharing the information online since at least 2011 and the article I shared was research from 2009, (G3.101), – so the clock is ticking on how soon the evidence based medical research will reach the individual patient who is in pain. The racers at the starting line are the physicians and nurse practitioners and other health professionals who make recommendations for opioid medications in an attempt to block pain instead of trying to find and resolve the cause of the pain.

What is a nerve signal? “Pain” or “no pain”? or “on” and “off”?
Pain, however, should not just be blocked without trying to understand the cause. It is a message from the body desperately asking for help but it is not always a clear message. Pain in one area of the body may have to do with an issue in another area of the body. Instead of blocking the pain signals we need to listen to them more carefully and try to figure out what the pain signals mean and how to resolve the underlying cause of the pain. Something might be missing and need to be added back into the diet or something might be happening in excess either in the diet or lifestyle habits and need to be stopped or moderated.

Nerve signals are not specific to send the brain a message of “pain” that exclusively means “pain;” a nerve signal is more of an “on” or “off” and might indicate a variety of extremes: too hot or too cold, or too rough or too light (ticklish), or too hot peppery, (capsaicin, (G3.100), more on that later), or too mustard oily. The nerve signal is simply telling the brain that “something” happened – figure it out captain of the ship – and fix it – such as remembering to wear gardening gloves before handling wild mustard weeds, especially if you have diabetic hypersensitivity.

The TRP channels are the bridge between the world and the nerve signal. There are many types and they can respond to specific temperatures, so some might activate when it is very cold and some might activate when it is very hot. Some might react to the hot pepper and some might react to the mustard oil. They would all tell the same nerve – “something” extreme happened.

Mustard oil can cause an extremely itchy reaction. It is used to induce “hypersensitivity” in lab animals to study the condition in relation to diabetic hypersensitivity. This will be discussed in the next section in more detail. (G3.96) Wearing gloves may be advisable when pulling a patch of wild mustard if you tend to have sensitive skin or allergic reactions.  (p124, G3.97)

Antihistamines taken daily can be helpful if excess histidine is a problem.

Antihistamines taken as a daily precaution may be helpful for people with overly sensitive skin if the sensitivity is related to a tendency to overproduce histidine. (G3.29) If that is an issue, then taking an antihistamine medication daily may also help for some types of chronic pain as well, more will be included in the next section. Acupuncture is a traditional therapy that may help reduce the overactivity of TRPV channels and reduce the production of the inflammatory peptide Substance P and other cytokines. Acupuncture can affect both the opioid and the cannabinoid receptors – but without needing the prescription or having to experience the side effects! (G3.104)

See a healthcare provider for medical advice, diagnosis or treatment.

  • Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References:

G3.5: Negative stress chemicals may cause symptoms like itching, migraines, pain or IBS.

Our bodies don’t have specific receptors just for sensing “pain.” Pain is a sign that something is wrong in the body and is sensed in a variety of ways. In medical terminology there are two main types of “pain.”

  • Nociceptive pain is associated with physical damage to the body or by sensations of pressure or heat or extreme cold. It might be due to pressure from a cancer tumor. Nociceptive pain might be described as “sharp, aching or throbbing.”
  • Neuropathic pain is caused by physical damage or pressure on nerves. It might also be due to a cancer tumor but one that is pressing on a nerve. Nerve damage can also be due to some nutrient deficiencies such as vitamin B12,  (G3.13), or other “Nutritional imbalance, alcoholism, toxins, infections or auto-immunity.” Neuropathic pain often is described as “a burning or heavy sensation, or numbness along the path of the affected nerve.” (G3.14)

Some types of pain such as migraine headaches may involve both nociceptive pain due to the pressure of inflammation or dilation of blood vessels an neuropathic pain from pressure on nerves by dilated or inflamed blood vessels.

    The next part gets complicated, some background information:

  • Calcitonin is a hormone released by the thyroid that promotes lower blood calcium levels by reducing bone resorption, (G3.15) (Bone resorption: breakdown of the bone and release of minerals, (G3.16)).
  • Calcitonin Gene-Related Peptide 1 and 2 (CGRP 1: (G3.17) and CGRP 2: (G3.18)) cause dilation of blood vessels in the heart and brain and throughout the body. Its prevalence in the Central Nervous System (CNS) also suggests that it may also have a neurotransmitter or neuromodulator role.

CGRP is produced by nerve cells in the brain and throughout the body. The protein has a role in sensations of pain. It is a member of the calcitonin family of proteins and exerts its effects at receptors that are formed from two other types of receptors.

The CGRP protein has two commonly found forms, one helps reduce pain and one helps increase it – luck of the draw. The alpha form of the protein may help reduce pain while the beta form is associated with migraine, temporomandibular joint (TMJ) pain, psoriasis and irritable bowel syndrome (IBS). The beta form is largely produced in keratinocytes found in the epidermis layer of skin. The alpha form is the type produced more within sensory nerves. (G3.19) (Psoriasis is an eczema-like condition believed to be autoimmune in nature.)

After a physical injury like a bump on the shin, inflammation causes an increased output of the Calcitonin Gene-Related Peptide (CGRP) and an inflammatory protein that is called Substance P, possibly for peptide, which is another word for protein. The release of the peptides follows shortly after an inflammatory event and shortly the chemicals are released there is  edema and plasma leakage in the surrounding area. (G3.20) The inflammatory peptides are also released in increased amounts during migraine headaches. (G3.21) The peptides increase the dilation of blood vessels and cause increased leakage from blood vessels (edema) and “degranulation of mast cells.” (G3.19) (G3.21)

Levels of CGRP increase in people who suffer from migraines and a type of prescription medication, called sumatriptan, which has been found helpful to stop migraine pain, has also been found to inhibit the release of CGRP in migraine patients. The medication may be inhibiting the release of CGRP by increasing intracellular levels of calcium. The “cytokine TNF-α” may be involved in migraine pain. (G3.21)

That was the background – the bottom line – magnesium deficiency can make the body more susceptible to the negative effects of CGRP, Substance P and chronic stress. And a chronic stress situation combined with chronic magnesium deficiency may lead to the development of inflammatory conditions like migraines, fibromyalgia, PTSD, or Irritable Bowel Syndrome. The magnesium deficiency associated with the inflammatory peptides CRGP and Substance P may be causing an increase in the level of the cytokine TNF as early as two days after a deficient diet was begun in a research study with lab animals. (G3.22)

So an Epsom salt bath or foot soak may relieve itch by providing the body with a form of magnesium that can be absorbed through the skin bypassing any GI problems that might underlie a chronic magnesium deficiency. It isn’t uncommon to have a diet low in magnesium but it is also not uncommon in the food supply. Problems with poor absorption or increased kidney or bowel loss are common causes of chronic magnesium deficiency.

A variety of tips for reducing Substance P levels are included in the article Trichodynia, Pain, and Substance P. Exercise, hobbies that use repetitive motions of the hands such as knitting, and stretching exercises may help reduce excess levels of the inflammatory chemical according to the article on the website drwardbond.com, see the article for more details: (G3.23)

See a healthcare provider for medical advice, diagnosis or treatment.

  • Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References: