Strategic Mindset & Grit – try, try, try again, but a little bit better each time.

Strategic Mindset – thinking critically about goals and outcomes, and whether methods are working or need to be modified. (1)

Grit – sticking with a tough problem or a long complex job. (1)

Having grit without a strategic mindset might leave you eventually all tired out but not at the goal you might have hoped for. Keep trying, but check the progress and redirect the craft as needed to get you to where you want to go. Trying to row a boat across a rapid river requires rowing slightly upstream against the current or you will just be pushed downstream. (1)

Our choices can make us healthier, wealthier, wiser, more productive, and feeling better about ourselves. Or they may lead to chronic illness and feeling unproductive, tired and listless, and it might seem difficult to go to work or look for a job, or to study for that important test or new job skill.

Support can help us stick with the difficult choices and tasks, or or negative, lack of support, may make us give up or feel like we can’t accomplish our goal. If someone is consistently negative to you, let it go, that is them, your choices are you. This also may mean letting go of well meaning advice that was intended positively, yet doesn’t match your goals, or you already had learned the suggestion didn’t work for you.

  • Don’t try to win over those who ridicule, mock or hate. You’re not called to be the jackass whisperer.” -Scott Stratten

Health or lifestyle habits can be generally helpful for most, but we are individuals and health habits may not all be as helpful for each of us in the same way. Tuning into our own needs can help us learn what seems to lead to feeling energetic and happy and what tends to add to the tired and listless, or headachy and irritable.

  • Our self-respect tracks our choices. Every time we act in harmony with our authentic self and our heart, we earn our respect. It is that simple. Every choice matters.” – Dan Coppersmith

Sometimes the grit might be needed to wade through the deluge of information available to us in our modern virtually connected world, to find the nuggets that will be of most value for our own needs. The information in a book can help you plan a strategy that might get you to your goal, it won’t get you there while it stays in the book though. You have to try the techniques, and practice and modify the strategy, refining it as needed until it is effectively helping you to reach your desired goal.

  • Information is not knowledge. The only source of knowledge is experience. You need experience to gain wisdom.” ~ Albert Einstein
  • We are drowning in information but starved for knowledge.”  – John Naisbitt
  • “There seems to be an inherent eagerness of this next-gen workforce to avoid starting from scratch, but to seek out the best of what exists and build upon it. This may be a condition of pressure put on them earlier in their career to produce results and solutions at a more rapid pace than has ever been expected before. Companies would be wise to harness this energy and, through technology, give them better and more instant access to those building blocks. ” – KeySafety (

Nutrition science – we need all the building blocks to build health, enough of each in balance with the others to support a stable structure.

Experience knows how to create a stable structure from the rudimentary knowledge.
(Image found online, original source unknown, via @ProfFeynman .)

Practice makes perfect it is said, but not if what you are practicing is not a good technique for you, or in general.

  • In theory there is no difference between theory and practice. In practice there is. -Yogi Berra (via @nonludic)

Knowledge is collected from Experience that is shared by others or that you had learned first hand by trying something, whether once or with ongoing practice until the skill was mastered. Creativity can take that information and imagine new ways to look at it, and Wisdom may see connections that others didn’t see.

Knowledge is collected from Experience shared by others or learned first hand.
Creativity can take that information and imagine new ways to look at it,
and Wisdom may see connections that others didn’t see.
(Graphic found online, original source unknown, via @ThinkingWiseman.)

What creativity and collective wisdom did it take the ancient people who created Stonehenge as a giant astronomical calendar to get the circle of stones in alignment with the passing stars? That is hard to imagine, or how the giant stone blocks were cut and moved by hand.

Sunrise at Stonehenge today (17th January) was at 8.02am, sunset is at 4.32pm, “
Image by Stonehenge, U.K., @STONEHENGE.

In building anything we need perseverance, grit, to stick with the hard work that might take years or decades to accomplish. To build effectively we need to have a strategic mindset with a plan that may be adapted along the way as methods are tested and analyzed for whether the goal is being achieved. Did the planets and stars move across the skies at the time the stone circle indicated or was modification in their placement needed? Stonehenge was initially likely a circle of smaller bluestones before all the large stones were moved from much farther away and put in place. It would have been arduous work. You wouldn’t want to have to move one of those building blocks again if you goofed.

  • The oldest part of the Stonehenge monument was built during the period from 3000 to 2935 bce. … Although it once was believed that the Aubrey Holes served as pits for wooden posts, excavation and archival research by the Stonehenge Riverside Project revealed that they probably held Welsh bluestones.” – Stonehenge- First stage: 3000–2935 BCE (Britannica)

The first stage of building Stonehenge took the ancient people about 65 years, the second stage about 160 years, third, about 190 years, and the fourth, fifth, and sixth stages of building are estimated to have been completed over another 760 years. That is quite a dedicated community project. (Britannica)

The reason why Stonehenge was built is not known, however having a calendar, even a really, really large one, may have helped with determining when to plant crops to maximize yield. There was a change in climate conditions for about 700 years during the time Stonehenge was built which made growing crops more difficult and herd animals became more predominant until the cold weather improved. (sciencenewsforstudents)

To build health we need all of the nutrient building blocks and it can be helpful to have phytonutrients and other complex molecules in our diet too. Nucleotides are needed to make the RNA that is needed for us to make each protein molecule such as bitter taste receptors. We may be able to make nucleotides but there would also be some in animal product foods. It saves us energy to use ready made molecules that are small enough to be absorbed whole. Colorful plants and vegetables have many phytonutrients and phospho-nutrients that can help us directly or may be used as building blocks to help us build other molecules.

Studies on cognitive health, our mental fitness as we age, have found that the modern Western diet has adverse effects while a more Mediterranean style diet was more protective. People whose diet was estimated to be the most like the Mediterranean diet, had cognitive health equivalent to being 5.8 years younger than those with the least Mediterranean style diet.

  • Western diets may adversely affect cognitive health,” Agarwal said. “Individuals who had a high Mediterranean diet score compared to those who had the lowest score were equivalent to being 5.8 years younger in age cognitively.” – Unhealthy Foods May Diminish Diet’s Positive Effects, January 8, 2021,, (

The Mediterranean Diet has anti-inflammatory benefits from the olive oil, which is rich in monounsaturated fats, and the diet tends to include a generous amount of fish and other seafoods regularly which would be a good source of omega 3 fatty acids. The Western diet uses a lot of plant/seed oils which are high in polyunsaturated fats and omega 6 fatty acids both of which can increase inflammation when eaten in excess. The ratio of omega 3 to omega 6 fatty acids is too low in the modern diet due to the use of refined plant oils like canola seed, corn or soy oil.

The Mediterranean diet also tends to have more beans, with smaller servings or less use of meats, than the Western diet. The phytonutrient rich herbs like oregano and basil might be used in far greater quantity along with other healthy vegetables and fruits than in the standard Western diet.

Another study looked at the effects of different diet patterns on the muscle mass of a group of Australian women. Interestingly The ‘plant focused‘ diet was not associated with skeletal muscle size while a traditional diet based on the Australian Recommended Food pattern was linked to muscle mass and an overall use of fewer inflammatory food and beverage choices was also. People on the ‘plant focused‘ diet may not have been getting enough protein or other nutrients involved in our production of muscle tissue.

  • Three a posteriori dietary patterns were identified from the PCA and named: i) plant-focused, ii) western, and iii) traditional. The plant-focused pattern was characterised by positive factor loadings on fruits, vegetables, legumes, fish, nuts, rice, tofu, yogurt, red wine, and eggs, and negative loadings on white bread. The western pattern included positive factor loadings on pizza, potato chips, processed meats (sausage, meat pies, salami, bacon), tomato sauce and pasta, and negative loadings on fruits. The traditional pattern was characterised by positive loadings on vegetables, jam, tinned fruit, red meat (beef and lamb), biscuits, ice cream, fish, and high-fibre cereals, with no negative loadings (Jacka et al., 2010).” – Diet quality and a traditional dietary pattern predict lean mass in Australian women: Longitudinal data from the Geelong Osteoporosis Study (Davis et al, 2021)

It takes knowledge to know which foods are more beneficial or less inflammatory, and it takes experience to try them and find out if they are also not inflammatory for your personal metabolism and health. It takes creativity to prepare interesting meals from a wide range of healthy foods, and wisdom to see the long term value in going to the effort to do so, most days. It also takes wisdom or strategic mindset to watch for patterns in your symptoms and health and modify your choices as you age or your health changes.

Every decade our metabolism slows down a little so we need about 10% less calories than we did in the previous decade – this would vary somewhat with the amount of physical and mental effort we expend and our personal thyroid hormone level and other factors.

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.

Reference List

  1. The Mindset You Need to Succeed at Every Goal.,
  2. Unhealthy Foods May Diminish Diet’s Positive Effects, January 8, 2021,, (
  3. Jessica A. Davis, Mohammadreza Mohebbi. Fiona Collier, et al., Diet quality and a traditional dietary pattern predict lean mass in Australian women: Longitudinal data from the Geelong Osteoporosis Study. Preventive Medicine Reports, Vol 21, March 2021, 101316,

COVID19, summary of nutrients that might help prevent, treat, recover.

I had untested Covid19 like illness Feb/March prior to when testing was available. Antibody testing wasn’t available until 3 months later and it was negative at that time. My symptoms and timeline matched the description of the still novel illness. Due to my autoimmune illness history I already was familiar with and using daily, many phytonutrients, in addition to other nutrients.

I managed to get better on my own but the symptoms got into breathless asthma like problems with non-productive cough before I started recovering and my history of colitis-like/inflammatory bowel symptoms also flared up but I was also familiar with what foods could help get that back under control instead of worsening. Severe diarrhea can be deadly too and a percentage of Covid patients did have bowel symptoms too, see the pomegranate peel section below for a link. (More specifics on my illness: Treatment vs a ‘Cure’.

Twenty two other nations besides the United States are distributing medications, nutrients, and/or therapeutics, for early at home treatment for their citizens. (

Citrus Peel and Bioflavonoids

Patients could be helped with some non-toxic, inexpensive, readily available nutrients and phytonutrient foods. Bioflavonoids – citrus peel – was what I added to my routine as the non-productive cough got worse – within 10-20 minutes the mucus had loosened and my airways opened and I could cough it out. Vitamin C, chewable 100 mg (what I had), also soothed my sore throat and helped with breathing. The serving of citrus peel to open the airway (lots of research on bioflavonoids for asthma exists) that I found helpful was about 2 teaspoons of orange zest every few hours or one navel orange peeled with a sharp knife so the white pith was left on the orange instead of being removed. (citrus peel posts)

Powdered bioflavonoid is readily available for purchase in bulk and the inner pith is mild – it could simply be added to foods for patients still able to eat. Bitter taste receptors in the lungs are activated and cause thinning of the mucus, opening of airways, and increase in cilia moving the mucus up and out of the lungs. Bioflavonoids are also a source of some vitamin C, quercetin, and a variety of flavonoids that may also be available as single nutrients such as hesperidin and that might help patients who could only be given nutrients intravenously (Evaluation of the Intravenous and Topical Routes for Ocular Delivery of Hesperidin and Hesperetin). Like vitamin C, hesperidin and other flavonoids can help reduce risk of vascular problems. 

Niacin and other B vitamins have anti-viral power, and are needed to help with energy level and reducing inflammation.

equate B vitamins are also important for preventing vascular and other symptoms. Thiamin (needed in higher amounts during an infection, Operation Thiamine – Reducing the Need for Hospitalization of Patients with COVID-19.), riboflavin, and niacin also have anti-viral action. The niacin can be very effective at higher doses, given in the ‘flush’ form, building up to 1000 mg day. (Sufficient Niacin Supply: The Missing Puzzle Piece to COVID-19, and beyond?.) People with a methylation gene difference may be at more risk because the methylated folate and B12 are essential for homocysteine metabolism. Excess homocysteine is a cause of atherosclerosis. Sulfate and vitamin C are also needed for preventing excess homocysteine (Review: Chemical Pathology of Homocysteine. V. Thioretinamide, Thioretinaco, and Cystathionine Synthase Function in Degenerative Diseases)

Magnesium helps white blood cells kill infected cells & protects the brain from inflammation risks.

Epsom salt, magnesium sulfate, can be absorbed through skin pores (any studies about magnesium chloride not being that well absorbed have little to nothing to do with the absorbability of a hydrated magnesium sulfate molecule). The sulfate is bioactive and patients would also be helped by the magnesium. Magnesium is nature’s calcium channel blocker and so would help protect against cell damage from excess calcium being allowed into cells. Magnesium is also essential for white blood cells to be able to perform apoptosis, killing infected cells and removing them safely. Poor intestinal absorption is not uncommon and topical magnesium or intravenous may help, especially if muscle cramps are a symptom. Lab tests showing hypokalemia can also suggest low magnesium is a problem. (Mechanism of Hypokalemia in Magnesium Deficiency – JASN)

Magnesium also is needed as a calcium channel blocker to protect against stimulation by EMF energy which can also open the calcium channels. (Klinghardt pdf) See post: EMFs and Intracellular Calcium – Magnesium is nature’s calcium channel blocker. For the long hours of sleep in particular it can help reduce inflammation risk to remove or turn off WiFi devices from the sleeping area or nearby rooms. Various products are available that block EMF such as cell phone cases and modem covers which help reduce excess energy release, ( Router Guards) turning it off while sleeping would be ideal if possible.

The SARS-CoV-2 virus can add viroporins to the infected cell’s membrane which allows calcium to enter. The excess calcium within a cell causes the creation of NLRP-3 inflammasomes which produce cytokines that increase inflammatory changes in other cells, (“pro-inflammatory IL-1β cytokines“). (Klinghardt/3/19/2020,pdf) The viroporin channels vary somewhat for different virus and one type is blocked/inhibited by the anti-viral medications “amantadine and rimantadine.” (viroporins) Adequate magnesium would help protect other cells if/when an infected cell burst open to release the newly replicated virus from the infected cell. Phytonutrients that may help inhibit NLRP-3 inflammasome assembly are listed towards the end of this post: Phytonutrients that may help against SARS-CoV-2.

Avoiding EMF exposure would help by not adding more activation of our own calcium channels and promoting even more entry of excess calcium into all of our cells (our whole body being exposed to the EMF somewhat equally depending on the source, or more to our ear/hand if holding a smartphone). (Klinghardt/3/19/2020,pdf)

Blackout curtains or an eye mask for sleeping or napping can help with eye sensitivity and may help the body make more melatonin which has protective effects against viral infection and inflammasome production. Vitamin C also reduces inflammasome production and can reduce over negative effects on blood vessels. (Klinghardt/3/19/2020,pdf)

Zinc helps us make antibodies and immune cells, and has antiviral power when given with a zinc ionophore.

Zinc is needed to make mature T-cells and for the thymus gland to make antibodies. Zinc is needed for the gene transcription of bitter (and other) taste receptors. Patients who have lost their sense of taste and smell may be experiencing zinc deficiency. Zinc is involved in protein replication and zinc ionophores are antimicrobial because of the ionophore carries the zinc to cells with excess iron (sign of infection or cancer) and help the zinc enter the cell where the zinc then disrupts protein replication – so no virus will be made. The current nutrient guidelines for zinc are likely half what an elderly person needs to promote thymus gland function. During an acute infection more can be given safely but high dose zinc can accumulate so is not for long term use. ( (other nutrients that may promote T-cells)

Zinc ionophores that have been found effective in many other nations of the world include hydroxychloroquine and ivermectin. Hydroxychloroquine has been safe and effective if given within the first few days to week of symptom onset and ivermectin has been found helpful in preventive, early treatment, and later stage treatment. Phytonutrient zinc ionophores that I was using anyway include quercetin and EGCG from pomegranate peel (my primary source – it is a main research interest of mine) or green tea. ( peel – anti-COVID19, may block ACE2 receptor access to the SARS-CoV-2 virus)

  • Ivermectin, a zinc ionophore, has helped in South America and elsewhere, review.
  • Hydroxychloroquine is also a zinc ionophore and has also been found effective given early with zinc and azithromycin: study .
  • Quercetin and EGCG are phytonutrient zinc ionophores that also have shown some benefit as antivirals against SARS-CoV2 and are available in foods and as herbal supplements.

Zinc is also needed for beneficial intestine microbes. Poor gut health has been linked to severe COVID19.

Zinc is also critically important for having a healthy microbiome – intestinal bacteria that help us instead of harming us. Beneficial species use as much as 30% of the zinc from our diet and if our daily diet is consistently low in zinc then more harmful species that don’t need zinc will grow instead. (Chronic Dietary Zinc Deficiency Alters Gut Microbiota Composition and Function, ) Poor gut health has been linked to more severe COVID19. (New Research Shows Poor Gut Health Connected to Severe COVID-19 – Probiotics May Help Patients)

Vitamin D deficiency has been found in as many as 80% of patients with severe COVID19 – it is needed for immune function & reducing risk of an over reaction that is inflammatory & can lead to long term autoimmune disease.

Vitamin D has been clearly shown to be a factor in severe COVID19 (an early study, April 2020) and it is unclear to me why the population as a whole is not being encouraged to take vitamin D and zinc right away – both are needed before an infection ideally. The vitamin D helps reduce risk of an autoimmune type cytokine over-reaction and the zinc is needed to make antibodies and help T-cells to change from immature to functional.

Studies … show an increased risk of infection in those with low vitamin D levels and a 25 to 30-fold reduced risk of ICU admission and a substantial reduction risk of death in older COVID-19 patients supplemented with vitamin D.” ~ Dr. Dan McCartney

Vitamin D and SARS-CoV-2 infection—evolution of evidence supporting clinical practice and policy development, McCartney et al, 2020. (quote via @mercola)

Low vitamin D levels has been associated with a greatly increased risk of death from severe COVID-19. Levels of vitamin D above 33 ng/ml seems most protective and the greatest risk seen with levels below 27 ng/ml according to one study. (Raharusun et al, an early study, 4/2020)

Low vitamin D levels were significantly associated with increased risk of death from severe COVID19 illness. Levels above 33 ng/ml seem most protective against mortality risk.
Results of the age-adjusted clinical study by the working group of Dr. Prabowo Raharusun,” Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study, an early study, 4/2020.

Standard nutrient guideline dosing of vitamin D may be adequate for protection but it needs to be prior to exposure to the infectious pathogen. Defense doesn’t help as much after an allergic/autoimmune over-reaction already developed. A review found that moderate dose supplements in advance helped reduce risk of respiratory infection by as much as 50%, while mega dose supplements of vitamin D taken after the respiratory infection had already begun were not significantly helpful. (Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data) The vitamin D3 form is more bioactive than the vitamin D2 form that is more typically available in one-a-day type supplements, if you have a choice about what to buy.

Pomegranate peel has anti-viral effects, a zinc ionophore and other phytonutrients that have brain protecting effects, and it can help intestinal health.

Pomegranate peel is a good source of hydrolysable tannins which can be healing to mucus membranes/GI tract) in smaller amounts and an irritant in larger amounts, also a diuretic, so dosing does matter – but I had colitis like flare-up with my CoV-like illness and my bean soup with a little pomegranate peel and Gumbo file was very soothing. The second half of this post has a list of hydrolysable tannin sources and mucilaginous foods or seasonings, which include Gumbo file: ACE2, Diarrhea, & COVID19 – it gets complicated.

Selenium deficiency is also more common in patients with severe COVID19.

Selenium deficiency has also been associated with more severe COVID19. Iodine is needed for immune function but I haven’t seen a direct finding of deficiency associated with severe CoV19. Vitamin A deficiency causes lack of immune function but excess conversion to active retinoic acid within the liver may be a factor in LongCovid – I have improved my health post CoV by reducing beta-carotene foods and I already had cut out all animal products during a previous autoimmune flare-up which helped. At the time I suspected I had developed an albumin autoimmune problem but maybe vitamin A was involved. I am still reading on this topic, very complex (Retinoid Toxicity)

Omega 3 fatty acids are anti-inflammatory and may help protect against death from COVID19.

Omega 3 fatty acids are the type found in fish oil, known also as EPA and DHA, and precursor, ALA, found in plant sources such as walnuts, flax seed meal and Black Currant Oil. Patients with severe COVID19 who had higher levels of omega 3 fatty acids had lower risk of dying of the infection than people with lower levels. ( Omega 2 fatty acids EPA and DHA have been found to be made into a endogenous cannabinoid form that has anti-inflammatory benefits. (Emerging Class of Omega-3 Fatty Acid Endocannabinoids & Their Derivatives)

Post recovery may have fatigue from anemia of chronic inflammation and worse symptoms may involve overproduction of the active form of vitamin A – retinoid toxicity.

The liver changes that lead to overproduction of active vitamin A can occur with Epstein Barr viral infection. I had mononucleosis in high school and chronic fatigue type symptoms since then, off and on. Post recovery this March I was still extremely fatigued and it felt like anemia of chronic inflammation/infection to me and I added artemisinin twice a day as an iron chelator and it helped within just a day or two, I was able to start going on short walks outside instead of feeling like the bedroom to the kitchen was too much exercise. (Artemisinin, arteannuin-B, sgp130Fc and COVID-19

Pain hurts. Health is better. We need all of the nutrients for health and in much greater amounts for some during illness. During health we make the antioxidant equivalent of 300 oranges – during illness we may no longer be able to do so, but we can’t eat 300 oranges, two teaspoons of citrus peel would have more antioxidants than one orange.

Resources with dosing recommendations for early or preventive self care by medical groups or professionals.

Regarding dosing for supplements – see an individual health care provider for individual guidance and here are some recommendations by medical groups or medical professionals:

  • Immediate Treatment for Early Stage SARS-CoV-2 Infections Recommended To Be Supported Nationally Starting Now,  Authored by Ben Kaplan Singer, M.D.; Daniel Stickler, M.D.; Avery J. Knapp Jr., M.D.; with many contributing doctors.  (googledoc)
  • TCM Treatment of COVID-19, based on extensive experience in Chinese hospitals, by Adam Tate, March 20, 2020, updated March 25, 2020. ( — This document includes a description of the progressive or varying stages of COVID19 illness. It includes examples of symptoms that occur in the different stages, and herbal recipes recommended for the specific stage and symptom set. The Chinese medical professionals have found that a combination of the traditional medicinal herb mixtures and modern medicines to be more effective than either alone for treating patients with more severe COVID19 infections. 
  • EVMS Critical Care COVID-19 Management Protocol, Developed and updated by Paul Marik, MD (17)
  • The Zelenko Protocol with over-the-counter self care and clinician guidance for the medication dosing is available here: Zelenko Protocol. For prevention: Zelenko COVID-19 Prophylaxis Protocol.
  • Dr Klinghardt’s COVID-19 Prevention & Treatment Guidance Summary, (website/to download pdf) (pdf) (summary pdf)
  • Physician Secrets Revealed: Outpatient Treatment For Covid-19, By Peter A. McCullough, MD, MPH (

A graphic summary of care guidance said to be used in Australia was shared on a social media site (harley_carter1). The protocol recommends Ivermectin, zinc, doxycyline, Montek-LC, Paracetamol for fever (better known as acetaminophen in the US). However I am unsure of the specific origin other than the site on the screen shot: (

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

Magnesium- protects against vascular calcification

Summary – Calcification is damaging throughout the body, not just in the kidneys, and magnesium can help reverse calcification but intestinal absorption of the magnesium may be a problem, increased urinary or sweat losses may also be a problem, and/or low protein and low phospholipids in the diet or inability to make the chemicals endogenously may limit the amount of back stock of magnesium that the body can store. Background info: We can not have excess magnesium in the electrically active ionic form (or other ions). Extra magnesium is held in a non-electrically active form on protein transport molecules and the phospho-chemical ribonucleotide ATP. Other nutrients and bitter tasting plant phytonutrients may also be needed to prevent calcification – vitamins D and K, magnesium, iodine, selenium, zinc are discussed in this post.

Magnesium, in particular, is a nutrient essential for vascular health & prevention or reversal of vascular calcification (VC).

Magnesium helps for prevention and reversal of vascular calcification (VC) – plaque build up along vessel walls of deposits of calcium and cholesterol which leads to stiffening and dysfunction of the vessels. Cholesterol buildup in the blood vessels was wrongly blamed exclusively on fat in the diet and cholesterol from eggs initially and people were instructed to not eat eggs and other cholesterol rich foods but we can make our own cholesterol too, and eventually it was recognized that excess carbohydrates was also a causal factor of vascular calcification. It has also been shown that excess calcium (or phosphorus) in ratio to magnesium availability may also be a primary causal factor of VC; and lack of other trace minerals, zinc, iodine, selenium, or vitamin D (12) can also be risk factors for vascular calcification.

Calcification in renal tissue or other organs of the body would cause dysfunction in different ways – disrupting the function of that organ type. Calcification of soft tissue and blood vessels is typically a problem associated with aging but it is seen early in life for young patients with chronic kidney disease on dialysis treatments and greatly increases risk of early death due to heart disease. (17)

Medial calcification is associated with increased vascular stiffening and cardiac workload, poor coronary perfusion, and sudden cardiac death and is thought to be responsible for the high cardiovascular mortality observed in [Chronic Kidney Disease] CKD patients.4 Significantly, even children and adolescents on dialysis develop vascular calcification and have a vastly elevated risk for cardiovascular mortality when compared with the normal age-matched population. Strikingly, the risk in adolescence is equivalent to that of the very elderly in the general population. 25” (17) *Medial calcification causes stiffening of the vessel wall but does not include plaque deposits that obstruct the interior of the blood vessel. (18)

Chronic kidney disease (CKD) afflicts more than 10% population and is becoming a major public health problem worldwide (Denic et al., 2016Yang et al., 2020). The prevalence of CKD in the elderly reaches to 14.3–41.3% in some countries (Susnik et al., 2017). CKD is also an independent risk factor for cardiovascular complications and all-cause mortality.” (19)

Both calcium and magnesium are electrically active minerals and the body has many methods to try to keep the levels of the minerals in a narrow range within the blood or cell fluid. Magnesium is kept at higher levels within cells and calcium has higher levels within the blood stream and extracellular fluid. Magnesium within cells helps inhibit calcium ion channels from opening and allowing calcium to enter from the surrounding tissue fluid.

Magnesium has inhibitory roles for several types of receptors and ion channels and within the brain. Other plant phytonutrients and vitamins, minerals, free amino acids, and nucleotides like ATP can also act as signals to cells and receptors on the cell surfaces, such as bitter taste receptors. Taste receptors can be found on the surface of immune cells, not just on the tongue, they are also found within the kidney and in the cells of the intestinal lining.

Membrane receptors can act like a lever – activate the lever on the outside of the cell and changes occur in the shape of the protein on the inside of the cell that lead to other actions occurring such as gene transcription of a specific protein type – so bitter taste receptors found in areas of the body besides on the tongue tend to be functioning as biologic machines that cause action besides a nerve signal to the brain saying “tastes bitter, don’t eat too much“. Within the kidneys bitter taste receptors can be activated by bitter tasting alkaloid phytonutrients and cause more uptake of calcium for removal in the urine output, more is included later in the post on this topic.

Cytokine types can lead to inflammatory actions or anti-inflammatory actions depending on the type. Cytokines are chemical signals that can be released by one cell to cause a change in another cell or in the original cell. Cytokines can act as signals to immune cells to activate a change in the function or type of cytokines it releases.

Magnesium prevents osteogenic vascular smooth muscle cell transdifferentiation in in vitro and in vivo models.” (1)

Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear.” [Vascular calcification (VC)] (2) .

TRPM7 is a magnesium membrane ion channel that is involved in embryologic development of the heart and kidneys. The TRPM7 ion channels also are involved in regulation of gene expression with the actions of an intracellular protein kinase domain. (3, 5)

Interleukin-18 is a cytokine that may be released by macrophages, dendritic cells, or the adrenal gland. It is involved in fighting infection and preventing cancerous tumor cell growth and may be increased by other stress conditions that activate the adrenal gland. Elevated levels of IL-18 lead to longer episodes of non-REM sleep which is deeper sleep and may help reduce stress effects on the body. Osteoblast produced IL-18 suppresses osteoclast bone cells, which break down bone. (7) The role of IL-18 in inflammation does seem unclear.

Renal cellular senescence (alive but stop cell division and growth of new cells) and premature aging theory of early kidney disease.

Increasing evidence indicates that there is a striking similarity between the manifestations of progressive [Chronic Kidney Disease] CKD and aging kidney (Docherty et al., 2020Goligorsky, 2020Zhou et al., 2020). As such, CKD is often viewed as a form of premature and accelerated aging. Aging and CKD also share many common triggers and underlying mechanisms, such as cellular senescence, oxidative stress, inflammation, mitochondrial dysfunction, RAAS activation and hyperactive Wnt/β-catenin (Sturmlechner et al., 2017Xiong and Zhou, 2019). In various animal models and human kidney biopsies, accumulation of senescent cells in different renal compartments is increasingly recognized as a common pathway leading to premature aging and CKD (Docherty et al., 2019Docherty et al., 2020).” (19)

Children receiving renal dialysis treatment were found to have DNA damage, reduced repair of damaged DNA, and faster than normal cellular senescence in samples of their vascular smooth muscle cells. Increased calcification and osteogenic cell differentiation was also found. Medications that blocked a type of DNA damage signaling reduced both the inflammation and the calcification. Question – why are they having DNA damage and reduced repair, and accelerated cellular senescence?

Vascular smooth muscle cells cultured from children on dialysis exhibited persistent DNA damage, impaired DNA damage repair, and accelerated senescence. Under calcifying conditions vascular smooth muscle cells from children on dialysis showed increased osteogenic differentiation and calcification. These changes correlated with activation of the senescence-associated secretory phenotype (SASP), an inflammatory phenotype characterized by the secretion of proinflammatory cytokines and growth factors. Blockade of ataxia-telangiectasia mutated (ATM)-mediated DNA damage signaling reduced both inflammation and calcification. Clinically, children on dialysis had elevated circulating levels of osteogenic SASP factors that correlated with increased vascular stiffness and coronary artery calcification. These data imply that dysregulated mineral metabolism drives vascular “inflammaging” by promoting oxidative DNA damage, premature senescence, and activation of a pro-inflammatory SASP.” (17)

Zinc deficiency causes problems with repair of DNA damage in an animal based study. “Zinc is an essential component of numerous proteins involved in the defense against oxidative stress and DNA damage repair. Studies in vitro have shown that zinc depletion causes DNA damage.” (20) Zinc has a variety of roles in renal health and in gene transcription and will be discussed more later in the post.

Hyperphosphatemia is more common in aging, and is a risk of Chronic Kidney Disease and dialysis treatment — it is also a cause of cellular senescence in muscle cells in an animal based study. “Hyperphosphatemia is an aging-related condition involved in several pathologies. … Knocking-down ILK expression increased autophagy and protected cells from senescence induced by hyperphosphatemia.” (21) Hyperphosphatemia in renal health and calcification will also be discussed more later in the post. Hypothyroidism and iodine are also discussed. Thyroid hormone is involved in the control of phosphorus levels in blood serum and excretion or retention within the kidneys. Either hypo or hyperthyroidism can affect phosphorus levels. (22) Perhaps a combination of nutrient related problems is leading to early kidney disease.

The Thyroid Hormone Receptor when activated by T3 Thyroid hormone can increase DNA damage, seen with hyperthyroidism in an animal based study. T3 hormone also activated the ATM/PRKAA protein kinase (23) of the same type that was elevated in the children with early kidney disease, mentioned in the earlier excerpt, (17) , though the actions then performed by the kinase may be different. Interesting – noted.

T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate–activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration.” (23)

Magnesium sulfate – Epsom salt can inhibit inflammatory cytokine production that can lead to bone matrix breakdown.

Adequate magnesium sulfate (MgSO4, Epsom salt) can help inhibit IL-6 and TNF-alpha production and was found to be linked to lower Nf-Kb levels. The magnesium working intracellularly seemed to be the causal factor for the reduction in inflammatory cytokine production rather than the sulfate (prenatal/preterm birth study). (4)

Vitamin K2 is also helpful with magnesium & calcium balance and reducing stress related bone loss.

When bone cells differentiate into osteoblasts or osteoclasts it is telling the bone matrix to either release calcium and magnesium and break down bone tissue, or to store more of it in new bone tissue (osteogenesis). So chronic low magnesium levels along with calcification of vascular and other soft tissue may also be due to inflammatory cytokines signaling more release of calcium and magnesium from the bones. Stress increases chemical stress on the body and can lead to weakening of the bones with increased osteoporosis changes. Adequate Vitamin K2 can help with calcium, vitamin D and magnesium metabolism and with bone health.

Vitamin K2 supplementation did help reduce calcification in an animal based study. “Arterialization, CKD, and vitamin K antagonism all significantly increased, whereas K2 supplementation attenuated calcification in healthy rats and rats with CKD.” (16)

Vascular calcification can also involve plaque deposits that obstruct the blood vessel.

Cholesterol and fatty deposits within the blood vessels may be more like the body trying to scab over excess calcium in a form that is no longer electrically active within the blood stream, rather than primarily or exclusively a problem of too much cholesterol or other fats in the diet. Calcium deposits and fatty deposits can be found in other tissue besides blood vessels, such as renal tubules and in vascular skin conditions such as calciphylaxis (previous posts/calciphylaxis) or calcinosis.

Screening for calcium in blood vessels may help predict who is more at risk for severe heart disease:

Analysing 52 previous studies, the international team of researchers found that people who have abdominal aortic calcification (AAC) have a two to four times higher risk of a future cardiovascular event. The study also found the more extensive the calcium in the blood vessel wall, the greater the risk of future cardiovascular events and people with AAC and chronic kidney disease were at even greater risk than those from the general population with AAC. Calcium can build up in the blood vessel wall and harden the arteries, blocking blood supply or causing plaque rupture, which is a leading cause of heart attacks and strokes.”

New research reveals early warning sign for heart disease. 14 January 2021 (24)

Causes of chronically low magnesium: certain diuretic medications, reduced kidney function, increased sweat loss, poor intestinal absorption, and low dietary intake.

Magnesium levels tend to be low in patients with kidney disease because of use of certain diuretics that cause magnesium wasting by the renal tubules, reduced function of the renal tubules at reabsorbing magnesium, and by low dietary intake. (1, previouspost) Patients with chronic kidney disease may be recommended to take a magnesium supplement three times per day equaling 1200 mg/day (15) which is about three times the RDA recommendation for normal health – chronic kidney disease is not normal health however.

Thiazide diuretics are a worse risk for magnesium wasting in the urine output (14) than “potassium-sparing diuretics such as amiloride.” (15)

Maintenance therapy may require oral administration of Mg2+ oxide (400 mg twice daily or three times daily) for as long as the risk factors for Mg2+ deficiency exist. Oral Mg2+ gluconate (500 mg twice daily or three times daily) can also be used. In addition, there are several slow-release Mg2+ preparations. As noted, is also important to address the underlying cause, and if diuretic therapy is being used, consideration should be given to the use of potassium-sparing diuretics such as amiloride, which can increase Mg2+ reabsorption in the cortical collecting duct. ” (15)

Subpopulations known to be particularly susceptible to the toxic effects of calcium include individuals with renal failure, those using thiazide diuretics (Whiting and Wood, 1997), and those with low intakes of minerals that interact with calcium (for example, iron, magnesium, zinc).”)

from: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride, Jan 1, 1997 (14) (nih-reports/previouspost)

Poor intestinal absorption of magnesium can be another reason for someone having low magnesium even though there is good magnesium sources in the diet.

Use of magnesium sulfate (Epsom salt) foot-soaks or baths might be a gentle and effective way to increase magnesium absorption for kidney or prenatal patients (or heart disease, diabetic, or cognitive patients) in a form that bypasses any intestinal malabsorption of magnesium. Calcium may be preferentially absorbed, especially if hormone/vitamin D levels are elevated. Posts on magnesium sources and role in health: 1) Epsom Salt Foot-soaks, 2) Magnesium – essential for eighty percent of our body’s chemistry. , 3) To have optimal Magnesium needs Protein and Phospholipids too., 4) Hypomagnesemia symptoms and causes list

Health requires all of the nutrients in a good balance with each other.

Excess calcium or excess vitamin D can lead to lower magnesium absorption and various negative symptoms. (previous post) Low magnesium may also be involved in the fatigue and mitochondrial dysfunction seen in fibromyalgia, as magnesium along with NAD+ is essential for mitochondria function. (6)

Patients with diabetes are more at risk for renal damage over time and also tend to be low in magnesium. Opioid pain killers do not provide pain relief for patients with diabetes unless magnesium was also given and a larger dose of magnesium reduced pain as much or more than the opioid plus magnesium intravenous dose. See post: G3.6.1.8: If magnesium deficiency is cause of a diabetic patient’s pain, why give opioids instead?. – excerpt from Stress & Relaxation a webpage that includes more information about TRP channels, magnesium and calcium, and their role in creating or reducing oxidative stress damage.

Renal health – kidney health – is a combination of adequate water, magnesium, potassium, and not too much total protein on average, and not excess sodium, calcium and phosphorus on average; as well as avoiding other kidney damaging toxins or chronically elevated blood sugar levels. Post: Make every day Kidney Appreciation Day. Other nutrients are also important for renal health including zinc, iodine, selenium, and vitamin D. For more on the topic of calcification, heart disease & magnesium, and vitamin D, zinc, iodine, and selenium see post: Links on heart disease, calcium and iodine, and/or

Iodine, Hypothyroidism, & the goitrogenic halides: fluoride, bromide, and chloride.

Excess fluoride, bromide, perchlorate, can interfere with iodine levels or replace it in a molecule if we have too little iodine. The fluoride, bromide, or chloride atom within the molecule wouldn’t function correctly. ( Iodine & Thyroid) The imbalance in iodine to other halide minerals (fluoride, bromide, or chloride) could increase hypothyroid symptoms without showing up as low levels of thyroid hormone so the problem might remain undiagnosed.

Hypothyroidism is more common among patients with chronic kidney disease than on average. “Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients…” (12) Trace mineral deficiency can affect other nutrients or minerals absorption or actions on the body. Selenium and iodine need to be in balance for optimal health. Deficiency of selenium is linked to increased risk of kidney disease. (11)

Phosphorus in excess can be damaging to kidney health.

Excess phosphorus intake whether from the diet (carbonated beverages would be a source) or from some types of dialysis treatments can increase vascular calcification, and also deficiency of vitamin D by reducing Sirt1 protein which has beneficial anti-inflammatory effects. (12)

Hyperphosphatemia induces [vascular calcification] VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.” (12)

FoxO’s transcription factors are downstream signals of Sirt1, and activation of Sirt1 induces FoxO3a expression to suppresses cellular ROS…” (12)

Zinc is needed for gene transcription of bitter taste receptors & other proteins.

Trace minerals share some mineral transport proteins which is why some minerals have more impact on the level of another one such as copper and zinc.

Zinc may also be important for healthy kidneys (and body) because of involvement in gene transcription as well as in enzymes. Zinc sulfate helped prevent renal calcification in an animal based study. “ZnSO4 increased the abundance of zinc-finger protein TNF-a–induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-kB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression.” (10)

Zinc is also necessary for the body to transcribe the gene for the protein that is made into bitter taste receptors (or other types of taste and odor receptors), so if a person has poor taste and smell sensation then they may also have low zinc levels and low levels of bitter taste receptors in the kidneys (and other areas of the body). See post: Zinc, cancer, and bitter taste receptors.

Bitter taste receptors in the kidneys & plant alkaloids

Why do we have bitter taste receptors in the kidneys? because when activated they increase the removal of calcium. Alkaloid plant phytonutrients (“phellodendrine and coptisine“) have been found to activate the renal taste receptors and increase uptake of calcium as a result. (8) Caffeine is also an alkaloid phytonutrient. (9)

Plants are the major sources of alkaloids, especially certain families of flowering plants, including Papaveraceae (poppy – [poppy seeds are a source]), Amaryllidaceae (amaryllis), Ranunculaceae (buttercups), Solanaceae (nightshades), and Stemonaceae.” (9)

The Solanaceae (nightshades) plants include tomatoes, white potatoes, eggplant, Bell peppers, tobacco, and several plants that have seeds or other plant material with toxic effects – Belladonna, Jimson weed, Nightshade, Datura, and Bittersweet. (images search results)

Phytonutrients used medicinally in Traditional Chinese Medicine and other herbal care practices are listed in this document with a few excerpts and notes: TCM and other phytonutrients for kidney health. Many medicinal herbs contain bitter tasting phytonutrients and often extracts of medicinal plants are made into medicines such as chloroquine from quinine tree bark. Quinine is an alkaloid derived from the bark of the Cinchona tree (Fig. 7.1). “ (13)

Baking to do list – make lemon zest poppy seeds muffins because I love them and they may be good for my renal health.

Team – magnesium sulfate, zinc, iodine, selenium, Vitamin D, protein, phospholipids.

Secondary take home point – while magnesium, and particularly topical Epsom salts (magnesium sulfate) may help reverse or prevent vascular calcification within the kidneys (and rest of the body) – other nutrients may also be essential to help in that process such as zinc, iodine, and selenium. Adequate vitamin D is also essential while excess may increase calcium excess and add to problems with poor intestinal absorption. Adequate protein and phospholipids are also necessary to maintain a surplus supply of magnesium within cells.

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.

Reference List

  1. Anique D. ter Braake, Marc G. Vervloet, Jeroen H.F. de Baaij and Joost G.J. Hoenderop. Magnesium to prevent kidney disease–associated vascular calcification: crystal clear? Nephrol Dial Transplant (2020) 1–9 doi: 10.1093/ndt/gfaa222
  2. Zhang K, Zhang Y, Feng W, Chen R, Chen J, Touyz RM, Wang J, Huang H. Interleukin-18 Enhances Vascular Calcification and Osteogenic Differentiation of Vascular Smooth Muscle Cells Through TRPM7 Activation. Arterioscler Thromb Vasc Biol. 2017 Oct;37(10):1933-1943. doi: 10.1161/ATVBAHA.117.309161. Epub 2017 Aug 31. PMID: 28860220.
  3. Jingjing Duan, Zongli Li, Jian Li, Raymond E. Hulse, Ana Santa-Cruz, William C. Valinsky, Sunday A. Abiria, Grigory Krapivinsky, Jin Zhang, David E. Clapham. Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proceedings of the National Academy of Sciences Aug 2018, 115 (35) E8201-E8210; DOI: 10.1073/pnas.1810719115
  4. Sugimoto J, Romani AM, Valentin-Torres AM, et al. Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J Immunol. 2012;188(12):6338-6346. doi:10.4049/jimmunol.1101765
  5. Demeuse P, Penner R, Fleig A. TRPM7 channel is regulated by magnesium nucleotides via its kinase domain. J Gen Physiol. 2006;127(4):421-434. doi:10.1085/jgp.200509410
  6. Yamanaka R, Tabata S, Shindo Y, et al. Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress. Sci Rep. 2016;6:30027. Published 2016 Jul 26. doi:10.1038/srep30027
  7. Interleukin 18 – an overview,,
  8. Liang J, Chen F, Gu F, Liu X, Li F, Du D. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells. Mol Cell Biochem. 2017 Apr;428(1-2):193-202. doi: 10.1007/s11010-016-2929-1. Epub 2017 Feb 24. PMID: 28236092.
  9. Chen C., Lin L. (2020) Alkaloids in Diet. In: Xiao J., Sarker S., Asakawa Y. (eds) Handbook of Dietary Phytochemicals. Springer, Singapore.
  10. Voelkl, J., Tuffaha, R., Luong, T. T. D., Zickler, D., Masyout, J., Feger, M., Verheyen, N., Blaschke, F., Kuro-o, M., Tomaschitz, A., Pilz, S., Pasch, A., Eckardt, K. U., Scherberich, J. E., Lang, F., Pieske, B., & Alesutan, I. (2018). Zinc inhibits phosphate-induced vascular calcification through TNFAIP3-mediated suppression of NF-kB. Journal of the American Society of Nephrology29(6), 1636-1648.
  11. Shuang Li, Qingyu Zhao, Kai Zhang, et al., Se deficiency induces renal pathological changes by regulating selenoprotein expression, disrupting redox balance, and activating inflammation. Metallomics, 2020,12, 1576-1584!divAbstract
  12. Lu C-L, Liao M-T, Hou Y-C, Fang Y-W, Zheng C-M, Liu W-C, Chao C-T, Lu K-C, Ng Y-Y. Sirtuin-1 and Its Relevance in Vascular Calcification. International Journal of Molecular Sciences. 2020; 21(5):1593.
  13. Quinine: an overview,,,for%20the%20treatment%20of%20malaria.
  14. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride, Jan 1, 1997
  15. Kevin J. Martin,  Esther A. González and Eduardo Slatopolsky, Clinical Consequences and Management of Hypomagnesemia,  doi: 10.1681/ASN.2007111194 (JASN November 1, 2009 vol. 20 no. 11 2291-2295)
  16. Cozzolino M, Mangano M, Galassi A, Ciceri P, Messa P, Nigwekar S. Vitamin K in Chronic Kidney Disease. Nutrients. 2019;11(1):168. Published 2019 Jan 14. doi:10.3390/nu11010168
  17. Pilar Sanchis, Chin Yee Ho, Yiwen Liu, et al., Arterial “inflammaging” drives vascular calcification in children on dialysis. Kidney International, Vol 95, Iss 4, April 2019, Pages 958-972
  18. Kin Hung Liu, Winnie Chiu Wing Chu, Alice Pik Shan Kong, et al., US Assessment of Medial Arterial Calcification: A Sensitive Marker of Diabetes-related Microvascular and Macrovascular Complications. Radiology 2012 265:1, 294-302,the%20arterial%20lumen%20(2).
  19. Xu Jie, Zhou Lili, Liu Youhua, Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies. Frontiers in Pharmacology, 11;2020, pp1898 DOI=10.3389/fphar.2020.601325 “Furthermore, hyperphosphatemia induced by Klotho depletion in CKD …”
  20. Song Y, Leonard SW, Traber MG, Ho E. Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats. J Nutr. 2009;139(9):1626-1631. doi:10.3945/jn.109.106369
  21. Sosa P, Alcalde-Estevez E, Plaza P, et al. Hyperphosphatemia Promotes Senescence of Myoblasts by Impairing Autophagy Through Ilk Overexpression, A Possible Mechanism Involved in Sarcopenia. Aging Dis. 2018;9(5):769-784. Published 2018 Oct 1. doi:10.14336/AD.2017.1214
  22. Ana I. Alcalde, Manuel Sarasa, Demetrio Raldúa, José Aramayona, Rosa Morales, Jürg Biber, Heini Murer, Moshe Levi, Víctor Sorribas, Role of Thyroid Hormone in Regulation of Renal Phosphate Transport in Young and Aged Rats, Endocrinology, Volume 140, Issue 4, 1 April 1999, Pages 1544–1551,
  23. Alberto Zambrano, Verónica García-Carpizo, María Esther Gallardo, Raquel Villamuera, Maria Ana Gómez-Ferrería, Angel Pascual, Nicolas Buisine, Laurent M. Sachs, Rafael Garesse, Ana Aranda; The thyroid hormone receptor β induces DNA damage and premature senescence. J Cell Biol 6 January 2014; 204 (1): 129–146. doi:
  24. New research reveals early warning sign for heart disease. 14 January 2021,,

From a previous post “Pomegranate peel/extract is also a source of EGCG. Pomegranate preparation tips and more information about health benefits is able on page Pomegranate. It may have anti-inflammatory activity through down regulation of Fox03a (4) which is a protein that can increase oxidative stress damage in mitochondria (5) where the NAD+ chemical reactions are taking place.”

  • 4. Liu S, Zhang X, Sun M, Xu T and Wang A: FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 40: 175-181, 2017
  • 5. Tseng AH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013 Oct;63:222-34. doi: 10.1016/j.freeradbiomed.2013.05.002. Epub 2013 May 7. PMID: 23665396.

12. Chien-Lin Lu, Min-Tser Liao, Yi-Chou Hou, et al., Sirtuin-1 and Its Relevance in Vascular Calcification. Int. J. Mol. Sci. 2020, 21, 1593; doi:10.3390/ijms21051593 “FoxO’s transcription factors are downstream signals of Sirt1, and activation of Sirt1 induces FoxO3a expression to suppresses cellular ROS…” (12)

Addition, new research about factors that indicate senescence occurring in cells after starvation time period rather than remaining in the quiescent stage of ongoing cell division: Same difference: Predicting divergent paths of genetically identical cells. Jan 11, 2021,