RBCs rouleaux formation, mineral deficiency.

Severe blood clotting after the 2nd jab is likely, especially with strong EMF and mineral deficiency. Increase in globulin proteins may be involved in the rouleaux, red blood cell stacking seen w GO & post jab blood smears.

Red blood cells from the same person before and after the CoV injections. (2)

Rouleaux formation (Red blood cells, RBCs, stacking like a tower of coins) happens more often in equine blood cells than human due to a difference in the strength of the electrical charge on the surface proteins. The sialic protein of their blood cells has a weaker negative charge – less strength to repel other negatively charged blood cells.

  • Horse red blood cells are thought to form rouleaux because they have decreased negative charge (altered zeta potential) on their red blood cells.” (1)

Video about the stacking effect after jabs, especially after the second. The narrative in French switches to English shortly into the video. (2) The rouleaux stacking of RBCs was more likely when EMF was present and the blood had low mineral levels. {*Magnesium has a protective effect against EMF activation of TRP calcium channels. post} The clotting was found to be so thick after the second shot that it was deadly. Blood doesn’t even flow from a finger stick when they take samples from a CoV double injected person. (2)

Erythrocytes account for about 66% of the manganese in whole blood, whereas the “buffy coat”–platelets and leukocytes–accounts for about 30%.” (3)

The buffy coat layer of the blood only makes up 1% of the total blood volume, (4), and red blood cells do not have mitochondria so the difference in manganese is likely the difference in mitochondrial MnSOD. The erythrocytes 99% of the blood, the RBCs, have 66% of the blood manganese, while the 1%, platelets and white blood cells have 30%. (3, 4)

Manganese Superoxide dismutase, MnSOD, is necessary for survival.

Lab mice and fruitflies bred to have a defective gene for making MnSOD did not survive. Mice with one of the two copies defective and one functional survive but are more at risk from oxidative stress.

  • Studies using mice (182) and fruit flies (40) demonstrated that MnSOD gene knockout is lethal; while MnSOD heterozygous mice with haplo-insufficiency can survive but are more susceptible to oxidative injury (169171). The crucial role of MnSOD in protecting cells against oxidative stress has been extensively studied and thoroughly reviewed (7589123130150161), pointing to the critical roles of MnSOD in maintaining cellular physiology in response to genotoxic conditions, such as oxidative stress.” (5)

Manganese may have been a causal factor in the UK outbreak of Mad Cow prion disease, CJDv.

Organophosphate chemicals can include metals and may have been a causal factor of Mad Cow Disease, however the research was suppressed in the UK instead of being further studied for confirmation. (6, 7) Toxic manganese can be one of the problem metals. (6)

My reply: I have been wondering if the graphene o. is affecting manganese in platelet’s mitochondria > rouleaux effect. and maybe that would cause the manganese to be in a dangerous form instead of beneficial as in the CJD research you linked to.

There has been a case of prion disease with an onset shortly after having CoV injections. (8) A COVID19 patient also had prion disease develop. (9) The spike protein may be a risk factor for prion disease developing. (10, 11)

  • On July 12, a second lumbar puncture came back positive for CJD — a prion disease. Cheryl’s tau protein value was 38,979 pg/ml, while the spectrum for CJD positive patients is 0 – 1,149.” (8)

The injection version of the spike protein was modified and may be more dangerous rather than less so. (15) The S1 subunit can separate and both S1 and S2 subunits may lead to misfolded proteins. The S1 part can be released free from the cell while the S2 part stays connected and the interaction with surface proteins may also be recognized as an autoimmune protein.

  • But it’s far worse, as the vaccines do not cause your body to make the same spike protein as SARS-CoV-2 but one that has been genetically modified, making it far more toxic.” – Long-Term Damage from COVID Vaccination (15)
  • Screening for prion disease in CoV injected people with symptoms is a plan in the works, contact person, Adam Gaertner https://twitter.com/veryvirology/status/1433968726609596420?s=19

Graphene oxide is stable chemically but may be involved in unusual physiology, if the system is chemically unstable due to EMF or mineral deficiencies. We don’t know what we don’t know.

Graphene oxide as an ingredient of the nano-lipoparticles in the injections may also be a factor in prion risk, (12), if it is effecting manganese in platelets. (6) Manganese superoxide dismutase and graphene oxide are reactive and combinations are being studied for medication use (13), and for industrial use. (14)

Booster jabs will likely keep increasing the risk of the severe RBC stacking reaction as it would be adding more graphene oxide with each dose. Clearing graphene oxide from our bodies may not occur readily as it is very stable chemically.

Mineral deficiency of magnesium or manganese may be a risk factor for the rouleaux effect.

EMF fields plus graphene oxide content in a mineral deficient person may be combined factors in the rouleaux effect seen in platelets of CoV injected patients. (2) Magnesium helps prevent calcium entry into cells or mitochondria which can overactivate them and cause harm if excessive, possibly caused by a strong EMF device. Deficiency would increase risk. Deficiency in manganese would also increase risk of oxidative stress within mitochondria as MnSOD is the main antioxidant within mitochondria. (16)

Excerpt from a paper about 5G EMF https://drive.google.com/file/d/1ojIE24GOLmSeDgImDdo_MH8Bcf7WU7KZ/view

Nrf2 deficiency may increase risk for lack of MnSOD as it promotes our production of the antioxidant.

Manganese superoxide dismutase is something we have to make for ourselves – and the increased need for it during increased oxidative stress explains the benefit of Nrf2 promoting nutrients mentioned in a recent post. The Nrf2 gene and protein promote our own production of MnSOD. (16) We would also need manganese, and magnesium. (17)

Early data suggests 3rd jabs are hockey sticking the death rate (exponential increase) (18):

3rd dose launched on July 30th“, @MConceptions (18)

An autopsy had to be personally paid for, as well as being demanded and sought out. The autopsy did show the sudden death was due to the CoV injections the person had been given. (19) How can we “Follow the science” if basic procedures such as autopsy is not being performed? And in the case of sudden deaths that are occurring during a medical experiment? All adverse events during a medical experiment should be studied in depth and recorded. Instead autopsy and research seems to be being prevented?

Illegal directives need to be resisted, not complied with, a unified show of resistance by the people is needed.

Unity and strength is needed. The way to fight illegal directives, not passed by Congress, or not Constitutional, is to not comply. An apology later is not going to help an injury, and is unlikely to appear. Teamwork by many, many people is the way to turn down the government or business direction to keep jabbing, or to have jab ID’S- the jabbed need to not accept a ‘privilege’ based on their status, and not participate in an apartheid system.

Image of an Immunization card that is cut in half – apartheid rules need to be resisted.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use.

Reference List

  1. Red Blood Cells/Patterns, eclinpath.com, https://eclinpath.com/hematology/morphologic-features/red-blood-cells/patterns/
  2. The Effects of Vaccination of the Blood, crowdbunker.com, https://crowdbunker.com/v/UGjH6zVYqM
  3. Milne DB, Sims RL, Ralston NV. Manganese content of the cellular components of blood. Clin Chem. 1990 Mar;36(3):450-2. PMID: 2311212. https://pubmed.ncbi.nlm.nih.gov/2311212/
  4. Human Buffy Coat, buypbmcs.com, https://buypbmcs.com/blog-human-buffy-coat/
  5. Candas D, Li JJ. MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxid Redox Signal. 2014;20(10):1599-1617. doi:10.1089/ars.2013.5305 https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3942709/
  6. Educating RIDA, westonaprice.org, https://westonaprice.org/health-topics/educating-rida/
  7. Mad Cow Disease, topic page, various links to follow, westonaprice.org, https://www.westonaprice.org/farm-and-ranch/mad-cow-disease/
  8. Megan Redshaw, Woman Dies of Rare Brain Disease Within 3 Months of Second Pfizer Shot, Doctor Says Vaccine Could Be Responsible. Aug. 31, 2021, childrenshealthdefense.org, https://childrenshealthdefense.org/defender/cheryl-cohen-dies-rare-brain-disease-second-dose-pfizer-covid-shot/
  9. Young MJ, O’Hare M, Matiello M, Schmahmann JD. Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration?. Brain Behav Immun. 2020;89:601-603. doi:10.1016/j.bbi.2020.07.007 https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7362815/
  10. Tetz, G.; Tetz, V. SARS-CoV-2 Prion-Like Domains in Spike Proteins Enable Higher Affinity to ACE2. Preprints 2020, 2020030422 (doi: 10.20944/preprints202003.0422.v1). https://www.preprints.org/manuscript/202003.0422/v1
  11. Idrees D, Kumar V. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration. Biochem Biophys Res Commun. 2021;554:94-98. doi:10.1016/j.bbrc.2021.03.100 https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7988450/
  12. Microscopia de vial CORMINATY, Dr Campra, Contaminants found in jabs, report: https://www.dropbox.com/s/jz513lflikwb403/MICROSCOPIA_DE_VIAL_CORMINATY_DR_CAMPRA_FIRMA_E_1_HORIZONTAL.pdf?dl=0
  13. Farell M, Self A, Guza C, et al., Lipid-Functionalized Graphene Loaded with hMnSOD for Selective Inhibition of Cancer Cells. ACS Appl. Mater. Interfaces 2020, 12, 11, 12407–12416, February 20, 2020, https://doi.org/10.1021/acsami.9b20070 https://pubs.acs.org/doi/abs/10.1021/acsami.9b20070
  14. Cheekati, S., Xing, Y., Zhuang, Y., & Huang, H. (2011). Graphene platelets and their manganese composites for lithium ion batteries. ECS Transactions, 33 (39), 23-32. DOI 10.1149/1.3589918 https://corescholar.libraries.wright.edu/math/405/
  15. Long-Term Damage from COVID Vaccination, undercurrents723949620.wordpress.com, https://undercurrents723949620.wordpress.com/2021/05/30/long-term-damage-from-covid-vaccination/
  16. Cofactors & Phytonutrients, see MnSOD, jenniferdepew.com, https://jenniferdepew.com/cofactors-%26-phyonutrients
  17. Nutrients, see Manganese and Magnesium, jenniferdepew.com, https://jenniferdepew.com/nutrients
  18. @MConceptions, “3rd dose launched on July 30th“, twitter.com, https://twitter.com/MConceptions/status/1433390269148418055?s=20
  19. Controversial Autopsy Reveals Link to COVID Vaccine. thehighwire.com, https://thehighwire.com/videos/controversial-autopsy-reveals-link-to-covid-vaccine/

https://media.giphy.com/media/4hTXbtsp0I8bHwY7cW/giphy.gif?cid=790b7611d231af726382d512cca541e9a154d36128749d59&rid=giphy.gif&ct=g

https://harvard2thebighouse.substack.com/p/our-lives-are-not-our-own

Aids, notes:

Epsom salt, magnesium sulfate, is a well absorbed form for topical soaks. Poor intestinal absorption can be a problem, especially if there is a gene difference in the TRPM6 ion channel gene.

Epsom salt soak, 20-40 minutes with a handful, one cup of magnesium sulfate
(a type of salt that isn’t Table salt, Sodium chloride).

4a. Self care strategies, effectivecare.info, https://effectivecare.info/4-1%3A-self-care-strategies

C19 Protocols: https://c19protocols.com/author/c19prot/

contaminants found in jabs, report: https://www.dropbox.com/s/jz513lflikwb403/MICROSCOPIA_DE_VIAL_CORMINATY_DR_CAMPRA_FIRMA_E_1_HORIZONTAL.pdf?dl=0

“COVID affects the intestines. Serotonin is mostly produced in the intestines. therefore, it is important to put in order the microflora (bifido + lactobacilli + broad-spectrum digestive enzymes) + add griffonia and orange, and berberine to eliminate inflammation.” – @bichikota https://twitter.com/deNutrients/status/1434494732227461120?s=20

“These studies demonstrate that baicalein attenuates mitochondrial oxidative stress by activating Nrf2-mediated MnSOD induction.” https://pubmed.ncbi.nlm.nih.gov/21787690/

Spike summary spreadsheet; telomerase, Circadian cycle & Nrf2

The spike protein may be rapidly increasing aging by affecting the length of telomerase, a topic discussed in a previous post with potential dietary/phytonutrient aids. EGCG and other nutrients that promote the Nrf2 gene or protein have protective effects growth and repair and immune function. In the process of reorganizing the Spike protein Risks & Aids – Summary List into a spreadsheet,* a pattern emerged in the various phytonutrient and other aids – they promote Nrf2 and inhibit NFkB along with the rest of the circadian cycle promoting lifestyle factors.

  • *Spike protein Risks & Aids – Summary List into a spreadsheet, * To read each box of the table click on the box and a drop down window should appear with all the text whether brief or a long list of references.
  • The vitamins, minerals, and TMG & DMG, have dosing details listed now on a new page of my jenniferdepew.com/nutrients site with dosing ranges and links for food sources and more info if interested.
  • I will add another page for the phytonutrients, antioxidants, and cofactors, or maybe a few pages. goals
  • Various covid19 protocols are listed on this site: https://c19protocols.com/author/c19prot/

*Addition – 8/30/2021 article about the senescence effect of the spike protein: Le SARS-COV2 accélérerait l’âge biologiqueSARS-COV2 would accelerate biological age, (FranceSoir), translated from French, written by a group that includes Nobel Prize winning scientist Luc Montagnie, (2008 Nobel Prize in Medicine) and Walter Chesnut whose work is included in earlier posts on this site; Xavier Azalbert, Anne-Typhaine Bouthors, Michel Brack, Dominique Cerdan, Walter Chesnut, Gérard Guillaume, Jean-François Lesgards, Luc Montagnier, Jean-Claude Perez for FranceSoir.

~

Modern life seems to be the underlying theme of what is a risk factor and what might help – return to more ancient darkness for sleep, get full spectrum light with UV for 15-30 minutes per day, in the morning hours of your day may be ideal. Adequate iodine and magnesium is needed to help the body not have a calcified pineal gland and the pineal gland is needed to make melatonin. Melatonin is needed for immune function and has a role in energy production and inflammation removal involving niacin and the Citric Acid Cycle. Melatonin can be taken as a supplement however, then your body may be even less likely to make its own – working on improving pineal health and nighttime darkness (eye mask if need be, but covering the skin is needed too, we can sense light with photosensitive skin receptors).

Metabolic Syndrome involves magnesium deficiency, which increases hypertension and insulin resistance. The Citric Acid Cycle uses glucose to provide ATP for cellular energy or to be released as heat by a special type of adipose tissue called brown fat. People living in cold climates who spend time in the cold tend to have larger amounts of brown fat then people living in warm climates. The niacin receptor is involved in ‘uncoupling’ the Citric Acid Cycle from producing ATP as energy storage units and instead releasing it directly as warmth. The heat and reddening of the skin during a niacin flush is an example of the release of energy as heat.

There are many cofactors necessary for the Citric Acid Cycle, the chemical pathways used by mitochondria for the release of energy from glucose. The cofactors almost all also are promoters of the anti-inflammatory Nrf2 pathways, although the levels of a few minerals are regulated by Nrf2. Excess copper or iron can be inflammatory. So making sure the diet has plenty of the food sources or supplements of all the various cofactors is helping the body remove inflammation directly within mitochondria to be released as a little extra warmth, and also to produce energy for cellular use, and your thinking and daily activity.

It may also be protective during times of infection to have adequate Nrf2 and Citric Acid Cycle capacity, and also adequate uncoupling capacity: adequate niacin and/or butyrate to activate the GP109 receptors that are involved in the mitochondrial energy uncoupling, so the excess energy from oxidative stress chemicals or free iron, can be released as fairly harmless heat instead of transferred to ATP molecules. The heat during a fever is from a different cause than the temporary warmth experienced after taking a high dose of niacin – which gets milder after having been using it for a while, and is milder when there is adequate melatonin present.

About the spreadsheet & reading it – the organization style.

This is the very initial stage of writing, and many of the references are new additions. I am sharing it early because it may help people and: Pain hurts, health is better, and health is worth some effort, even a lot of effort.

The spreadsheet has categories of What? is the problem, symptom, negative effect of the spike protein, in rows. Each category often had more than one and sometimes many aids that might help or be a negative factor, so the spreadsheet is extended into many columns so each aid or lifestyle factor could have its own individual column. The columns have an ‘x‘ for the category if it is an aid and there may be a note if the item is otherwise affected by the category. Some aids may help many types of problems, inflammation and direct anti-viral for example, so there would be an ‘x‘ in the inflammation category and an anti-viral category. Each box in the columns has references about that aid and how it relates to the category. Eventually this will be useful for writing an organized reference list and document or app of some sort.

Yes this is complex, not just one or two supplements to take – breaking news – life is a miracle, it is amazing that any of us function at all. Given that, we do know a lot about what might help prevent illness or chronic degeneration, if we are allowed to put it into individual self care practice. Individualized care means – Pay attention to what seems to help and stick with that, possibly with breaks occasionally or rotating things over days, weeks or months, in season or what seems particularly good at that time.

Rotating favorites can be protective, or herbal supplements too maybe. Sensitivities to foods or substances are more likely to occur with something eaten every single day or very often. On average wheat and corn, eggs and dairy are in foods commonly eaten at every meal.

Other nutrient supplements are needed daily because they are water soluble. Some are found in many common foods and generally are rarely deficient – except during times of severe malnutrition or infection – thiamine, B1, is one of those. Vitamin C needs are also incredibly increased during severe infection or inflammation, in part because our own production of antioxidants is reduced, we normally make far more than we would ever get from a vitamin C food or capsule (equivalent to 300 orange’s worth of vitamin C, approximately per day for normal health, but glutathione and other antioxidants).

The B vitamins and C are water soluble and magnesium is readily lost in sweat and urine so we need that daily similarly to potassium and sodium, like an electrolyte – to help maintain good fluid balance. We also need calcium regularly but the bones are storage account for both magnesium and calcium so an acute or chronic deficiency is less obvious than for sodium and potassium. Very acute magnesium deficiency can occur during strenuous exercise on a hot day, and cause death from a stroke. Ischemic stroke led to death due to any reason more often in hospitalized patients with lower magnesium levels, than for those with higher levels. (ref)

Via @DGrouf Dr Grouf

Early or preventive treatment for viral infection, per Dr. Grouf.

via Dmitry Katz, PhD: Niacin, NA, within a cell, graphic. The green oval is an endolysosome, (hopefully removing spike protein), and it is complex… :-)

Niacin helps with endolysomes which are like grocery or garbage sacks for engulfing cellular debris or pathogens to be processed into usable nutrients or waste removal. (Reference needed) via https://twitter.com/SantaKlauSchwab/status/1376187499584704513?s=19

Protocol by Dmitry Katz, PhD focuses on melatonin and recommends a high dose of it. There may be a risk that a person starts making less of their own. Focu

Also using blackout curtains at night with no little lights or alarm clock, or using an eyemask during sleep can help us make our own melatonin. Supplements might be useful if there was a lack of sleep night. The melatonin helps the niacin flush reaction be milder. I have found high dose niacin helpful, see an earlier post https://transcendingsquare.com/2021/01/22/niacin-early-treatment-in-general-for-sars-cov-2-is-sensible-reduces-hospitalization-and-mortality-rate/ for more information, and some precautions.

Niatonin Protocol by Dmitry Katz, PhD, *His website: niacincurescovid.com.

How to get started on the niacin part of the protocol and cautions about potential side effects and medications that may increase risk of side effects is available in this post: Niacin, & early treatment in general for SARS-CoV-2 is sensible, reduces hospitalization and mortality rate. Jan 22, 2021.

Disclaimer: Information shared for educational purposes within the guidelines of Fair Use. It is not intended as individual health guidance, please see a health care professional for individualized guidance. ‘Functional medicine’ practitioners work to restore normal function, nutritional adequacy and modify other lifestyle factors that might be part of a health problem.

Reference List

  1. You S, Zhong C, Du H, Zhang Y, Zheng D, Wang X, Qiu C, Zhao H, Cao Y, Liu C, -F: Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute Ischemic Stroke Patients. Cerebrovasc Dis 2017;44:35-42. doi: 10.1159/000471858 https://www.karger.com/Article/Abstract/471858

Nrf2 and Nf-Kb pathways – one restorative, one inflammatory

Many phytonutrients and other chemicals have been found to promote the production of the Nrf2 gene and its encoded Nrf2 protein, both of which have varying impacts on other genes causing an increase in immune strength and in our own production of antioxidants. Other research has focused on nutrients and chemicals that inhibit or promote the inflammatory Nf-Kb pathway – a chemical cascade of reactions starting outside the cell and ending in the cell with an increase in the cell’s production of inflammatory cytokines and Tumor Necrosis Factor (TNF).

The foods and chemicals often interact with both pathways but in opposite directions, promoting one and inhibiting the other. The reason is unlikely to be a coincidence, the night/day rhythms of circadian biology also tend to promote one and inhibit the other. The Nrf2 growth/repair/detoxification system is more active during sleep/dark and the NF-kB action/inflammation pathway is more active during the wake/light hours. See 1.4, 1.41, 1.42 in this draft book to read more: Preventative Health for Multifactorial Disorders.

Nrf2 Promoting Foods & Phytonutrients:

See G10: Nrf2 Promoting Foods, effectivecare.info for the reference in the graphic (Sun 2017) and more food ideas and information.

Nrf2 Promoting Foods and Phytonutrients

Neurotransmitters also vary in activity level due to the circadian cycle and can affect whether the Nrf2 or the NF-kB pathway is more active.

The neurotransmitters and neuromodulators mentioned in the last post are part of the circadian biology rhythms. Acetylcholine, attention and memory neurotransmitter, (Pepuo 2004), is more active during the day and GABA the calming neurotransmitter is more active at night. It is inhibitory, reducing activity of other neurotransmitters such as norepinephrine and serotonin that are active during wakefulness helps the body move into sleep. Low levels of GABA are associated with insomnia and disrupted sleep (Siegel 2004), and with anxiety, chronic stress, depression, difficulty concentrating and memory problems, muscle pain and headaches, and substance use disorders. (3 AmazingBenefits of GABA/PsychologyToday)

GABA which is known to have antioxidant and anti-inflammatory benefits may achieve it in part due to increasing the Nrf2 pathways growth, repair, and detoxification activity and by inhibiting the NF-kB and Caspase 3 pathways. (Zhu 2019) Resveratrol was found to help protect endothelial cells in animal models of Type 2 Diabetes and aging. It reduces oxidative stress by increasing the Nrf2 pathways, “improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring Caspase 3 activity and DNA fragmentation). (Ungvari 2010)

Lycopene is a phytonutrient that can help reduce inflammation by promoting the Nrf2 and inhibiting the NF-kB pathways.

The antioxidant lycopene was used in a study for use as a food additive in animal feed to help reduce oxidative stress caused by heat stress. The research team were concerned about the negative effects of heat stress on the Nrf2 and Nf-Kb pathways, causing decreased activity of the Nrf2 and increased activity of the Nf-Kb pathway. A brief description of the roles in the body is in the abstract: “The transcription entity nuclear factor-kappa light chain enhancer of B cells (NF-κB) controls the expression of genes involved in a number of physiological responses, including immune inflammatory responses, acute-phase inflammatory responses, oxidative stress responses, cell adhesion, differentiation, and apoptosis. The nuclear factor-2 erythroid related factor-2 (Nrf2), the redox-sensitive transcription factor, plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes.  “ (1)

Several carotenoids in addition to lycopene also reduce inflammatory pathways and increase beneficial ones.

Lycopene is a carotenoid, one of a group of red and yellow colored antioxidants found in carrots, cantaloupe and other fruits and vegetables that tend to be orange or red in color, The best known carotenoid is beta-carotene, a form of vitamin A that is made with two of the vitamin A retinol molecules. Other carotenoids, including beta-carotene, lutein, alpha-cryptoxanthin, and zeaxanthin, also can inhibit the NF-kB pathway and increase the Nrf2 pathways, reducing inflammatory cytokine production and increasing beneficial antioxidant production. Other phytonutrients that also increase the Nrf2 and inhibit the NF-kB pathways include:

Other phytonutrients that inhibit inflammatory and promote anti-inflammatory pathways:

  • sulforaphanes and I-3-C, from broccoli sprouts, broccoli, kale, mustard greens, turnips and other cruciferous vegetables,
  • andrographolides (and other diterpenoids – found in Gingko biloba, sage, rosemary, (sciencedirect/diterpenoids)), andrographolides are found in the medicinal plant Andrographis paniculata, (Okhuaroba 2014),
  • quercetin found in “leafy vegetables, broccoli, red onions, peppers, apples, grapes, black tea, green tea, red wine, and some fruit juices“, (integrativepro.com) ,
  • curcumin from turmeric,
  • silymarin, an extract from milk thistle, a medicinal herb,
  • genistein from soy,
  • chlorophyll, the green pigment in plants, and
  • resveratrol, found in “grapes, wine, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.” (lpi.oregonstate.edu)
  • (See 1.42, Preventative Health for Multifactorial Diseases)

That list is a start, there are other beneficial phytonutrients that decrease inflammatory pathways and increase anti-inflammatory pathways, including: ginger/zerumbone/gingerol, green tea/EGCG/gallic acid, garlic/aged garlic extract, hot pepper/capsaicin, fish oil/omega 3 fatty acids, black pepper/piperine, Hops/xanthohumol, Plumbago auriculata/plumbagin, a medicinal herb used for lead poisoning. (de Paiva 2005) (Sun 2017) (Gupta 2010)

Protecting health over the long term and every day can be as simple as adding more variety of herbs and spices to your meals, along with more colorful fruits and vegetables and whole grains, nuts, beans, and seeds.

That list is a start, there are other beneficial phytonutrients that decrease inflammatory pathways and increase anti-inflammatory pathways, including: ginger/zerumbone/gingerol, green tea/EGCG/gallic acid, garlic/aged garlic extract, hot pepper/capsaicin, fish oil/omega 3 fatty acids, black pepper/piperine, Hops/xanthohumol, Plumbago auriculata/plumbagin, a medicinal herb used for lead poisoning. (de Paiva 2005) (Sun 2017) (Gupta 2010)

Protecting health over the long term and every day can be as simple as adding more variety of herbs and spices to your meals, along with more colorful fruits and vegetables and whole grains, nuts, beans, and seeds.

Colorful and flavorful foods can help keep the body more in the restorative Nrf2 pathways and reduce the inflammatory NF-kB pathway. The same nutrients or chemical groups effect both because the pathways are coordinated by the light/dark wake/sleep circadian cycle and share a need for the same type of protein – as if both need the same tool – they both can’t use it exactly at the same time. (CREB protein, see section 6: Li, 2008)

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual health guidance. Please see a health care professional for individualized healthcare guidance.

References

  1. Sahin K, Modulation of NF-κB and Nrf2 pathways by lycopene supplementation in heat-stressed poultry, World’s Poultry Sci J Vol 71, Issue 2, June 2015 , pp. 271-284 https://www.cambridge.org/core/journals/world-s-poultry-science-journal/article/modulation-of-nfb-and-nrf2-pathways-by-lycopene-supplementation-in-heatstressed-poultry/4E2AFAAFDF88B0B438BE3A19A1FB0A9B

Hypercoaguability; TNF alpha & Nrf2

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

Localized hyercoaguability & granulomatous sarcoidosis.

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

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

Calcium excess, magnesium deficiency and hypercoaguability.

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

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

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

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

TNF alpha and the NF-kB Pathway

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

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

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

Flavones are a type of Flavonoid

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

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

Onions and Green Tea – ECGC

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

Orange Zest – Tangeritin

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

Vinpocetine

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

Long term steroid use may also increase coagulation risk.

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

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

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

Dehydration

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

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

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

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

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

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

Take Home Points

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

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

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

References

  1. Goljan-Geremek A, Geremek M, Puscinska E, Sliwinski P., Venous thromboembolism and sarcoidosis: co-incidence or coexistence?. Cent Eur J Immunol. 2015;40(4):477–480. doi:10.5114/ceji.2015.56972
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737745/
  2. Tarique Hussain, Bie Tan, Gang Li, et al., Modulatory Mechanism of Polyphenols and Nrf2 Signaling, Pathway in LPS Challenged Pregnancy Disorders, Hindawi, Oxidative Medicine and Cellular Longevity, Vol 2017, Article ID 8254289 https://pdfs.semanticscholar.org/7c94/3d7267998a159ed91162e7feea0092d3fffa.pdf
  3. D. Callaway, W. Jiang, K. Lingappan, B. Moorthy, Decreased Survival and Increased Oxygen-Mediated Lung Injury in Mice Lacking Nrf2: Protection by Beta-Naphthoflavone, American Journal of Respiratory and Critical Care Medicine 2019;199:A1158 https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A1158
  4. Beta-Naphthoflavone, MedKoo Cat#: 540310, medkoo.com,
    https://www.medkoo.com/products/15806
  5. Chan K, Kan YW. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A. 1999;96(22):12731–12736. doi:10.1073/pnas.96.22.12731,
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23072/
  6. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47. Published 2016 Dec 29. doi:10.1017/jns.2016.41,
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/
  7. Wardyn JD, Ponsford AH, Sanderson CM. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem Soc Trans. 2015;43(4):621–626. doi:10.1042/BST20150014
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613495/
  8. Jeon KI, Xu X, Aizawa T, et al. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci U S A. 2010;107(21):9795–9800. doi:10.1073/pnas.0914414107
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906898/
  9. Rachael Rettner, Dietary Supplement Ingredient Linked to Miscarriages, FDA Warns, livescience.com, June 4, 2019,
    https://www.livescience.com/65629-vinpocetine-supplements-miscarriages.html
  10. Hariri BM, McMahon DB, Chen B, et al. Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor. J Biol Chem. 2017;292(20):8484–8497. doi:10.1074/jbc.M116.771949
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437252/
  11. Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta. 2010;1799(10-12):775–787. doi:10.1016/j.bbagrm.2010.05.004
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955987/
  12. Chenyu Chu, Jia Deng, Yi Man, and Yili Qu, Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments, BioMed Research International, Vol 2017, Article ID 5615647
    https://www.hindawi.com/journals/bmri/2017/5615647/
  13. Higgins, Peter D.R., et al. Increased Risk of Venous Thromboembolic Events With Corticosteroid vs Biologic Therapy for Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology 2015: 13(2): 316-321, http://www.cghjournal.org/article/S1542-3565(14)01045-3/abstract
  14. Colburn S, Childers WK, Chacon A, Swailes A, Ahmed FM, Sahi R. The cost of seeking an edge: Recurrent renal infarction in setting of recreational use of anabolic steroids. Ann Med Surg (Lond). 2017;14:25–28. Published 2017 Jan 12. doi:10.1016/j.amsu.2017.01.015
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247564/
  15. Przybycinski et al., Renal Artery Thrombosis in a Bodybuilder using Anabolic Steroid – Case Report, J Sports Med Doping Stud, 2019, 9:1, DOI: 10.4172/2161-0673.1000215,
    https://www.omicsonline.org/open-access-pdfs/renal-artery-thrombosis-in-a-bodybuilder-using-anabolic-steroid–case-report.pdf
  16. Sarcoidosis & Your Organs, Cleveland Clinic,
    https://my.clevelandclinic.org/health/diseases/11865-sarcoidosis–your-organs
  17. Warning – Your Green Tea Isn’t What You Think It Is, Bottom Line Inc.,
    https://bottomlineinc.com/life/tea/warningyour-green-tea-isnt-what-you-think-it-is
  18. Suksamrarn S, et al., Xanthones from the green fruit hulls of Garcinia mangostana., J. Nat. Prod. 2002655761-763, April 17, 2002 https://doi.org/10.1021/np010566 https://www.ncbi.nlm.nih.gov/pubmed/12027762
  19. Fried LE, Arbiser JL. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid Redox Signal. 2009;11(5):1139–1148. doi:10.1089/ars.2009.2440 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842137/
  20. Emmanuel A.Ojo-Amaize, et al., Hypoestoxide, a Novel Anti-inflammatory Natural Diterpene, Inhibits the Activity of IκB Kinase, Cellular Immunology, Vol 209, Issue 2, 1 May 2001, pp 149-157,
    https://www.sciencedirect.com/science/article/abs/pii/S0008874901917988
  21. Choi HM, Jung Y, Park J, et al. Cinnamomi Cortex (Cinnamomum verum) Suppresses Testosterone-induced Benign Prostatic Hyperplasia by Regulating 5α-reductase. Sci Rep. 2016;6:31906. Published 2016 Aug 23. doi:10.1038/srep31906
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994048/
  22. Chen W, Lu Y, Chen G, Huang S. Molecular evidence of cryptotanshinone for treatment and prevention of human cancer. Anticancer Agents Med Chem. 2013;13(7):979–987. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625674/
  23. Cao Y, Chai JG, Chen YC, et al. Beneficial effects of danshensu, an active component of Salvia miltiorrhiza, on homocysteine metabolism via the trans-sulphuration pathway in rats. Br J Pharmacol. 2009;157(3):482–490. doi:10.1111/j.1476-5381.2009.00179.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707994/
  24. A. Ludwiczuk, et al., Chapter 11: Terpenoids, Pharmacognosy: Fundamentals, Applications and Strategies,  2017, pp 233-266,
    https://www.sciencedirect.com/science/article/pii/B9780128021040000111
  25. Terpenoids, Science Direct,
    https://www.sciencedirect.com/topics/neuroscience/diterpenoid
  26. Rayati F, Hajmanouchehri F, Najafi E. Comparison of anti-inflammatory and analgesic effects of Ginger powder and Ibuprofen in postsurgical pain model: A randomized, double-blind, case-control clinical trial. Dent Res J (Isfahan). 2017;14(1):1–7.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356382/
  27. E.M.Bartels, V.N.Folmer, H.Bliddal, et al., Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials., Osteoarthritis and Cartilage, Vol 23, Issue 1, Jan 2015, pp 13-21, https://www.sciencedirect.com/science/article/pii/S106345841401276X
  28. Ribel-Madsen, Søren; Bartels, Else Marie; Stockmarr, Anders, et al., A SynoviocyteModel for Osteoarthritis and Rheumatoid Arthritis: Response to Ibuprofen, Betamethasone, and Ginger Extract—A Cross-Sectional In Vitro Study., Arthritis, 2012, DOI: 10.1155/2012/505842
    http://orbit.dtu.dk/files/52967554/505842.pdf
  29. Herbal Medicines: Anticoagulation Effects, Open Anesthesia,
    https://www.openanesthesia.org/herbal_medicines_anticoagulation_effects/
  30. Xia Wangab, Xingrong Penga, Jing Lu, et al., Ent-kaurane diterpenoids from the cherries of Coffea arabica., Fitoterapia, Vol 132, Jan 2019, pp 7-11,
    https://www.sciencedirect.com/science/article/pii/S0367326X18307846
  31. Xin Zhou, Fengying Ren, Hong Wei, et al., Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats., Lipids in Health and Disease, 2017 16:239,
    https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0628-x
  32. Renata Nowak, Marta Olech, Natalia Nowacka, Chapter 97 – Plant Polyphenols as Chemopreventive Agents, 5.2 Phenolic Acids, Polyphenols in Human Health and Disease, Vol 2, 2014, pp 1289-1307, https://www.sciencedirect.com/topics/medicine-and-dentistry/gallic-acid
  33. Padhye S, Ahmad A, Oswal N, Sarkar FH. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs. J Hematol Oncol. 2009;2:38. Published 2009 Sep 2. doi:10.1186/1756-8722-2-38
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743703/
  34. Ginkgolide B, Science Direct, https://www.sciencedirect.com/topics/medicine-and-dentistry/ginkgolide-b
  35. Glycyrrhizin, Science Direct,
    https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/glycyrrhizin
  36. Halofuginone, Science Direct,
    https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/halofuginone
  37. Hematein, Sciencemadness Wiki, http://www.sciencemadness.org/smwiki/index.php/Hematein
  38. A promising target of anti-fibrotic therapy: herbal compound 861, EurekaAlert Science News, https://www.eurekalert.org/pub_releases/2008-05/wjog-apt091808.php
  39. Hydroxyethyl Starch, Science Direct, https://www.sciencedirect.com/topics/medicine-and-dentistry/hydroxyethyl-starch
  40. Zi-Ying Wang, Xin-Bing Wei, Lin Chen, et al., Neuroprotective Effects of Hydroxyethylpuerarin against Focal Cerebral Ischemia-Reperfusion in Rats., Chinese Journal of Physiology 50(5): 211-216, 2007 https://www.dropbox.com/s/t486fl5ieu1svjs/201412141532230.pdf?dl=0
  41. DiNicolantonio JJ, Liu J, O’Keefe JH. Magnesium for the prevention and treatment of cardiovascular disease. Open Heart. 2018;5(2):e000775. Published 2018 Jul 1. doi:10.1136/openhrt-2018-000775 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045762/
  42. Andrea Rosanoff, PhD, and Stella Lucia Volpe, PhD, RDN, ACSM-CEP, FACSM, Recorded Webinar: Modern Day Human Magnesium Requirements: The RDN’s Role, Today’s Dietitian, https://ce.todaysdietitian.com/node/69241#group-tabs-node-course-default1
  43. Karen Skene, Sarah K. Walsh, Oronne Okafor, Nadine Godsman, et al., Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia–reperfusion injury through depletion of glutathione., British Journal of Nutrition, Vol 121, Issue 9 14 May 2019 , pp. 961-973, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/acute-dietary-zinc-deficiency-in-rats-exacerbates-myocardial-ischaemiareperfusion-injury-through-depletion-of-glutathione/15953E00DA3E69629F36F9F6FE5079A8
  44. Karl T. Weber,1,* William B. Weglicki,2 and Robert U. Simpson3 Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium, Cardiovasc Res. 2009 Feb 15; 81(3): 500–508. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639130/
  45. Li YC. Vitamin D: roles in renal and cardiovascular protection. Curr Opin Nephrol Hypertens. 2012;21(1):72–79. doi:10.1097/MNH.0b013e32834de4ee https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574163/
  46. Benjamin Senst; Prasanna Tadi; Hajira Basit; Arif Jan., Hypercoaguability, STATPearls, Last Update: April 29, 2019. https://www.ncbi.nlm.nih.gov/books/NBK538251/
  47. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. 2016;8(2):68. Published 2016 Jan 28. doi:10.3390/nu8020068 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/
  • M Wang, W Liu, and T J Webster, Chapter 16: The Promise of Nano metals: Reducing Infection and Increasing Biocompatibility, Trace Metals and Infectious Diseases, Ed. Jerome O Nriagu and Eric P Skaar, Strungmann Forum Reports, (MIT Press, 2015, Cambridge, MA) https://mitpress.mit.edu/books/trace-metals-and-infectious-diseases
  • M L Ackland, J Bornhorst, F V Dedoussis, et al., Chapter 17: Metals in the Environment as Risk Factors for Infectious Diseases, Trace Metals and Infectious Diseases, Ed. Jerome O Nriagu and Eric P Skaar, Strungmann Forum Reports, (MIT Press, 2015, Cambridge, MA) https://mitpress.mit.edu/books/trace-metals-and-infectious-diseases
  • Wessels, I., H. Haase, G. Engelhardt, L. Rink, and P. Uciechowski, 2013. Zinc Deficiency Induces Production of the Pro-Inflammatory Cytokines IL-1beta and TNF alpha in Promyeloid Cells via Epigenetic and Redox-Dependent Mechanisms. J. Nutr. Biochem. 24:289-297. https://www.ncbi.nlm.nih.gov/pubmed/22902331