Tag: Sarcoidosis

Posted on

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
Posted on

Whether to be compliant or to be healthy seems like an easy question to answer

*I made a significant correction to this post today, so I’m moving it to the front page today.

— but it may not be that easy of a question for a patient of the current medical industry. Personally, I do like to be compliant and agreeable with other people but I also prefer to be healthy and agreeable rather than sick and agreeable. The terms compliant and non-compliant are used in the medical field when documenting how thoroughly a patient is following the recommendations of the medical team. However if the medical team’s recommendations are based on limited knowledge or incorrect information, then complying with the recommendations might not seem like a good idea to a patient. If an industry claims to not know what causes a disease or how to cure it then why should a patient be expected to believe that the same industry knows if a treatment will actually be adding to making the patient worse instead of helping them get better as is hoped? Some of their recommendations might be making the underlying, not well-understood, problem much worse.

The terms compliant and non-compliant may also be used in legal cases when there is conflict between a medical team’s recommendations and the parent’s decisions regarding the care of a child. Painful and possibly ineffective chemotherapy or other cancer treatments might be recommended to try to save a child’s life but if those treatments are just making the last few months, days, or years of the child’s life more miserable then who is being helped? The child and family are missing out on the quality  of life during their last days together and frequently with a significant financial cost. Paying for hope of a last chance cure at the cost of daily enjoyment seems like pretty expensive hope. The pharmaceutical industry’s profit margin may be helped but the child’s last days might be spent in more pain and nausea with less time to spend enjoying the company of their family.

Intravenous vitamin C has been used effectively against a variety of types of cancer at the Linus Pauling Institute for decades but vitamin C isn’t profitable because it can’t be patent protected. — A review article suggests there is some anti-tumor effects from the high dose intravenous vitamin C treatment but that it is not a miracle cure and is providing such a high dose, approximately 200 oranges worth twice a week, that it could be dangerous to a patient who had kidney problems. [8] 

Patents allow companies to charge higher prices for products because they are the only supplier. Generic products and natural products have market competition to help keep the price down for consumers.

A for-profit prison industry requires prisoners and tax-payer funding to finance their care and provide the profit, and a for-profit medical industry needs people to take medicine, whether they are sick or whether they are trying to prevent sickness. Requiring people to take maintenance medicine for chronic symptom control for years or for the rest of their life will add up to more profit for the medical industry over time compared to providing patients with effective preventive guidance or with a treatment that actually cures their underlying condition.

While I am fortunate not to have cancer I have been struggling with autoimmune and allergy symptoms for as long as I can remember and in my experience as a patient if currently available lab tests don’t reveal any diagnoses that are currently accepted within mainstream medical standards then your symptoms might be labeled psychosomatic – all-in-your-head physical symptoms that may be caused by mental stress or other emotional problems. That might be helpful for a patient who actually has psychosomatic problems but it isn’t very helpful for the long term treatment of a patient with an autoimmune disease.

Unfortunately though, in the current medical industry even if you receive an autoimmune diagnosis the cause is still considered unknown and immune suppressing chemotherapy drugs are frequently the only treatment available. However the good news is that the cause of some types of autoimmune disease has actually been discovered, but the news hasn’t made it into mainstream media or medical practice yet; and more good news, an effective therapy protocol has also been developed and life threatening chemotherapy drugs are not part of the medication protocol.

Severe migraine headaches every week were my worst health symptom, but I also had chronic fatigue and multiple muscle cramps similar to those described by patients with fibromyalgia, and I was sensitive to a variety of food and environmental allergens. I’ve only had a couple migraines since I tried the newly developed medication protocol. I spent a year and a half taking antibiotics every other day, and an angiotensin receptor blocker (olmesartan/Benicar) everyday, and avoiding vitamin D foods, supplements and sunlight everyday. This was not easy or comfortable, the antibiotics cause allergy like symptoms from the increased load of toxins that results from the remains of infected cells that healthy white blood cells were able to kill while on the combination of antibiotics and olmesartan, but the allergic symptoms were not as bad as having migraines that feel like a railroad spike pounding into your skull over and over for three days every week, never mind the muscle cramps, fatigue and other symptoms that I’d had off most of my life.

Not having weekly migraines and other daily symptoms was so wonderful that I wanted to share the good news but I found that it is difficult to get people to see past the mental block of “we don’t know what causes autoimmune disease or how to cure it.” — And we will never know what causes it or how to cure it if we keep ignoring the people who are making advances in figuring out what causes it and how to cure it.

Lida Mattman is a research scientist who conclusively showed that Rheumatoid arthritis is caused by a bacteria but that breakthrough hasn’t reached the patient yet. Some types of bacteria can survive in a modified form within the interior of some types of human cells. The form is hard to grow in normal agar gel cultures but Lida Mattman developed techniques that are able to culture the cell wall deficient microbes. She discusses the pathogens that cause Lyme’s Disease and Lou Gehrig’s Disease and other stealth pathogens at the Autoimmunity Research Foundation’s Chicago Conference, March 12, 2005, in this video link: (video, at ~19:30 she recommends not visiting people who had just suffered a coronary/heart attack in person at the hospital, just send a card, as evidence has shown that a infectious but unidentified pathogen is involved in some coronaries and therefore probably also in cerebral strokes which occur in the same way – but she probably doesn’t really mean not to visit your loved ones. She gets a laugh from the crowd as she shared a story about getting a sample to test after her husband had a coronary – so she probably did visit him but the point may also be that we don’t know what we don’t know and it might be dangerous, at least to the immune compromised).

Some types of pathogens, including the virus that causes HIV/AIDS, have forms that can actually enter human cells and survive and grow within the cell. This sets up an inflammatory condition with overactive white blood cells that may be looking for the infection but instead attack other healthy tissue – ‘auto-immune’ – attacking self. Lida Mattman found cell wall deficient bacteria involved in Rheumatoid Arthritis and Lyme’s Disease and other diseases. The bacteria that causes tuberculosis also has a form that can live within cells. The textbookofbacteriology.net site uses the term faculative intracellular parasite in their description of the pathogen that causes tuberculosis. [7]

The specialized pathogens developed ways to disguise the infected cells from healthy immune cells. The angiotensin receptor blocker medication olmesartan is normally given once a day for high blood pressure but for the auotimmune treatment protocol it is given three to four times per day every six to eight hours in order to keep the levels steady all day and night because the infected cells hide by developing angiotensin receptors – blocking the receptors takes away the disguise. I think – this is my rough understanding of how the medication helps in the protocol developed by Trevor Marshall, a biomedical engineer. Blocking the angiotensin receptor disguise somehow allows the healthy immune cells to identify and kill the infected cells instead of continuing to ineffectively attack other healthy tissue (such as finger joints in Rheumatoid arthritis or lung tissue in sarcoidosis).

Correction, (9/16/2015): The part about the angiotensin receptor blocker medication was wrong. The medication olmesartan (Benicar) is not only acting as a angiotensin receptor blocker (which can help reduce the production of inflammatory cytokines which cause pain and fatigue and can help prevent fibrotic tissue from forming). It also acts as an agonist, an activator, of the vitamin D receptors (VDRs). By activating the VDRs the medication is allowing the healthy immune cells to do their normal functions. The pathogens had developed a variety of ways to block the vitamin D receptors in order to ‘hide’ by disabling the immune cell’s normal immune functions that are controlled by the active VDR. It transcribes over 1000 genes that are involved not only in calcium balance but also in cancer metastasis and many other functions. MPKB: Science behind olmesartan (Benicar).

Prof. Marshall is not a medical doctor but he is a biomedical researcher who did not choose to be compliant when he was diagnosed with sarcoidosis and was told that he probably only had a year and a half left to live – over a decade ago. Instead he developed  his specialized medical protocol and then sought and received orphan drug approval by the U.S. FDA so that olmesartan/Benicar can be prescribed for use with the antibiotic Marshall Protocol in addition to it being able to be prescribed for its normal use for treating high blood pressure. Using the blood pressure medication three to four times per day may increase the risk of feeling light headed when standing up quickly but taking it 3-4 times per day doesn’t cause the blood pressure to drop 3-4 times lower than normal. (I did have to catch my balance occasionally and fainted once or twice while taking olmesartan three times per day for a year and a half. Fainting is weird but fifteen years of migraines is worse.)

A three day migraine or chronic arthritic degeneration seems worse to me than feeling light headed when standing up quickly – and the medication protocol isn’t needed for the rest of life as many medications are prescribed for patients with chronic illnesses. While the protocol reduces symptoms after a year or two on the medications, an autoimmune patient might need to follow Trevor Marshall’s protocol for a year or two more than once over their lifetime because autoimmune diseases tend to flair up and go in remission with the patient’s overall level of health or stress or environmental toxin load – there really is a lot we don’t know about autoimmune disease. Having good and bad times, remissions and relapses, may be common in autoimmune disease because just a few remaining infected cells may linger over the years and then multiply again during a stressful or otherwise unhealthy time of life.

Tuberculosis is a disease that has been shown to be caused by a type of bacteria able to live within human cells and the infection can be spread through air-borne respiratory droplets when actively sick patients cough or sneeze. The disease can remain dormant for years in healthy people and the sickness can be spread by people who never got sick themselves and therefore don’t realize that they are carriers. A continuing education session for health professionals recommends using Universal Precautions, in order to protect staff and to help prevent spread of infection between patients, health professionals are recommended to wear adequate masks and gloves and treat all patients as if they were potentially contagious because anyone might be a carrier of a dormant infection. The course, Infection Control and Prevention, Module 5, Element II: Mechanism of Transmission available at atrainceu.com [atrainceu.com] has more information about Universal Precautions.

“Every year, more than 9 million people worldwide develop TB and nearly 2 million people die from the disease. Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis and is spread in airborne droplets when people with the disease cough or sneeze. Most people with healthy immune systems infected with M. tuberculosis never become ill. However, the bacteria remain dormant within the body and can cause tuberculosis years later if host immunity declines.” – atrainceu.com, Infection Control and Prevention, Module 5, Element II: Mechanism of Transmission [atrainceu.com]

Tuberculosis, I learned recently, is also a type of infection that interferes with normal vitamin/hormone D metabolic pathways. The vitamin D receptor (VDR) plays a role in the ability of white blood cells to kill infected cells and cancerous cells. Some pathogens have developed ways to suppress the Vitamin D Receptor’s activity so white blood cells aren’t able to effectively resist the infection process. Other pathogens that have been shown to reduce the activity of the Vitamin D Receptor, in addition to the pathogen that causes Tuberculosis, include the mold Aspergillus, the viruses that cause Epstein-Barr chronic fatigue syndrome and HIV/AIDS, and the autoimmune diseases sarcoidosis, Crohn’s Disease, and Rheumatoid Arthritis. Elevated levels of 1, 25(OH)2D are seen with the bacterial infections: “Elevated 1,25(OH)2D appears to be evidence of a disabled immune system’s attempt to activate the VDR to combat infection.” [page 19, 1]

The Infection Control and Prevention course provides more information about Aspergillus. It is a fairly common mold that generally only becomes a problem for immuno-compromised individuals, [atrainceu.com], but interestingly those at increased risk also include people who have advanced cases of HIV/AIDS and those who have been on long term corticosteroid therapy (which acts similarly to having elevated levels of 1, 25(OH)2D, which is the active hormone form of vitamin D, and is actually not a vitamin. It is a seco-steroid based on a molecule of cholesterol). [2]

It seems to me that people with advanced cases of HIV/AIDs, whether they also have opportunistic aspergillosis or not, might like to know that taking olmesartan/Benicar daily and avoiding vitamin D foods, supplements and sunlight [1] might help their healthy white blood cells to be able to work more effectively again or might at least not add any negative symptoms that can occur when there is elevated levels of hormone D. The elevated hormone level itself is a health risk itself because it is telling the bones to release their stored calcium which can lead to osteoporosis of bones and calcification of soft tissue. The article [1]  doesn’t suggest that AIDS patients might be helped by Benicar because it is a review of research that has already occured article – research has shown that Benicar is helpful for autoimmune diseases like sarcoidosis but more research is needed to find out how the HIV and Epstein-Barr viruses and aspergillus mold suppress the Vitamin D Receptor and how to stop the down-regulation.

Our medical industry uses donated blood and organs that are screened for many diseases but they can’t screen for diseases that don’t officially have a known infectious agent. Dormant tuberculosis can cause carriers to become sick years after they were exposed and in all those years as a carrier the person might also have been a regular blood donor. Sarcoidosis patients who are in remission are allowed to donate blood and plasma yet there have been organ transplant patients who got sarcoidosis only after receiving the organ transplant. If the organ donor wasn’t known to have active sarcoidosis then the medical industry may not realize that the person might be a carrier of infected cells that could cause symptoms in a more immuno-compromised person. All organ transplant patients are purposely given immune suppressing medications in order to prevent the body’s own immune defenses from attacking the transplanted organ.

The longer autoimmune disease is treated as something without a known cause the longer we may be spreading it through contaminated blood and organ donations. The longer autoimmune disease is treated as something without a known cure the longer patients have to suffer reduced quality of life and shortened lifespans.

  • Tuberculosis: annually worldwide, 9 million infected and 2 million deaths, [atrainceu.com]
  • Epstein-Barr virus (EBV): According to the Centers for Disease Control about 90% of adults have antibodies against EBV, suggesting a current infection or history of exposure. The disease can be spread before a person has active symptoms and the virus can remain in a latent/inactive phase for years and can become active again at any time. [cdc.gov]
  • HIV/AIDS virus: According to the Centers for Disease Control there are about 50,000 people in the U.S. infected with HIV/AIDS each year and there are about 1.2 million people currently in the U.S. with an HIV/AIDS infection. About 12.8% of them may not be aware of their disease status. [cdc.gov]
  • Aspergillosis: According to the Centers for Disease Control the exact prevalence of opportunistic aspergillosis is unknown because it is not required to be reported in the U.S. however it is a common type of fungal infection found in organ transplant patients with a cumulative incidence of 19% over twelve months during a 2001-2006 study. It may also be a problem for up to 15% of patients with cystic fibrosis and 2.5% of patients with asthma, which represents 4.8 million people worldwide, 400,000 of whom might have a more severe form of aspergillosis.  There are 1.2 million people estimated to have aspergillosis as a complication of their tuberculosis disease and there may be 70,000 people who have aspergillosis as a complication of their sarcoidosis disease. [cdc.gov]
  • Sarcoidosis: According to a study of U.S. Navy personnel, “Sarcoidosis Among U.S. Navy Enlisted Men, 1965-1993,” the rate of disease incidence dropped over the time period but was significantly more of a risk for enlisted men who were assigned to aircraft carriers. The study was made at the request of a veteran who wondered if his case of sarcoidosis might have been due to an environmental contaminant.  “Although 70% of case-patients and 66% of controls had ever served on ships, 26% of case-patients and 17% of controls had ever served specifically on aircraft carriers.” (case-patients, n=1121) [3] *Living within the confined quarters of a ship or aircraft carrier may have affected risk of sarcoidosis infections if the disease can remain dormant similarly to tuberculosis. Exposure to the blood or body fluids of a seemingly healthy person might be able to be a source of latent infection for an immuno-compromised individual if the disease is carried within infected white blood cells.
  • Crohn’s Disease: I haven’t found statistics regarding the prevalence of this type of inflammatory bowel disease but the Mayo Clinic site at least mentions that an infectious agent might be involved: [4] Unfortunately they also recommend vitamin D and calcium supplements to help counteract the risk of osteoporosis if steroid therapy is used. [5] This would be bad if the patient actually has elevated levels of hormone D (1, 25(OH)2D) because levels above 42 pg/ml are a signal for calcium to leave the bones which ultimately increases the risk of osteoporosis and calcification of soft tissue. “In fact, there is ample evidence that elevated 1,25(OH)2D leads to bone loss. Brot et al. [53] found that elevated levels of 1,25(OH)2D were strongly associated with decreased bone mineral density and content, and increased bone turnover. When levels are above 42 pg/ml 1,25(OH)2D stimulates bone osteoclasts. This leads to osteoporosis, dental fractures and calcium deposition into the soft tissues [54]. Vanderschueren et al. [55] found that a combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.” [1] Adequate magnesium is very important when elevated calcium levels are a problem because it helps the kidneys to excrete excess calcium.
  • Rheumatoid Arthritis: Infection is also mentioned as a possible cause of Rheumatoid Arthritis on the Mayo Clinic site. [6]

That is an incomplete list of statistics but the point was that many people may be affected by pathogens that have developed ways to manipulate our immune system’s normal Vitamin D Receptor metabolism.

Trevor Marshall doesn’t recommend that people who are using his protocol with the help of their physician worry too much about what specific pathogens might be the cause of their own abnormal vitamin D/hormone D levels. Comparing the level of the inactive vitamin D, 25 (OH) D, with the level of the active hormone D, 1, 25 (OH)2D, can suggest infection when the inactive form is low but the active form is normal or elevated. Healthy individuals can remain at 30 pg/ml of the hormone while they are getting plenty of sun exposure and dietary supplies of the vitamin form. Elevated levels are not normal. Elevated levels during active autoimmune disease can be in the 100s while the vitamin level remains low and tends to remain low even when large dose supplements are taken regularly.

The problem is that the infection process has inhibited breakdown of the active hormone and/or causes over production of the enzyme that converts the vitamin into the hormone form so all the large dose vitamin is being converted into the active hormone form which wouldn’t be noticed if only the vitamin level was being measured by the lab – as is the routine currently. The hormone level is a more unstable form that is more expensive to process. The mainstream medical recommendation is based on the theory that the enzyme that can convert the vitamin into the hormone is under careful control by the kidneys, which may be true for healthy people but might not be true for someone with sarcoidosis or Rheumatoid arthritis.

Personal Impact

My own was hormone D level was 55 pg/ml recently which is within the range considered normal but it is towards the high end of the range. It has remained around that level even while limiting dietary sources and exposure to sunlight. The vitamin level was below 10 which is low, above 20 to 30 is the low end of the normal range for the vitamin form of D. So do I have low levels, normal levels or elevated levels?  My endocrinologist’s recommendation that was sent with the vitamin D/hormone D lab report was to start taking vitamin D and calcium in order to help reduce osteoporosis risk but if all levels over 42 pg/ml are causing calcium to leave my bones already then adding extra vitamin D is more likely to add to the infection risk. The use of Benicar and reduced intake of vitamin D and sun exposure is mentioned in this review article about Vitamin D and infection: [1]

My own medical history includes an episode of Epstein-Barr virus/mononucleosis during college and more recently a diagnosis of Grave’s Disease, which is an autoimmune thyroid condition related to Rheumatoid Arthritis in that bone marrow cells become labeled with a thyroid receptor and infiltrate the thyroid gland. The thyroid can become overactive and overproduce thyroid hormone and sometimes the bone marrow cells become mislabeled in a slightly different way and infiltrate the fatty area behind the eye sockets and cause the eyeballs to protrude. 

Professional Impact:

I would like professional guidance about abnormal vitamin/hormone D metabolism iin infection for myself and family and for feeling comfortable about counseling nutrition clients. Without knowing both the vitamin and hormone D levels of a client I can’t really know whether a low vitamin D level alone means the client isn’t getting enough of the nutrient or sun exposure or whether they might have an underlying infection that hasn’t been diagnosed. But without the professional ‘evidence-based’ guidance from the mainstream medical industry I can’t really recommend alternative strategies to a client legally. A professional code of ethics encourages us to do no harm in the health industry but during the earlier phases of medical research it can be more difficult to figure out what might be helpful and what might be harmful.

*I may add to this later but I’m going to try to post it now because I’m having trouble saving it. 2:12pm post was successful, update added, and at 10:54pm.

9/16/2015 correction added. A type of gastro intestinal bacteria, Prevotella copri, has been found to be more prevalent in the GI tracts of people with rheumatoid arthritis.  Intestinal bacteria linked to rheumatoid arthritis (Nov. 5, 2013).

This post is continued on the next two posts:

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

Posted on

Cell Wall Deficient Pathogens – L-Forms

Rheumatoid arthritis and other autoimmune diseases are actually the body’s attempt to find and kill human cells that had been colonized by pathogenic bacteria or fungi. At the microscopic level single celled organisms can exist in forms that are as different as the baby tadpole to the fully grown frog. During times of better health of the host the parasitic pathogen can change forms and hide from the better armed immune system within a few infected cells. During times of sickness, when there may be a flair up of the chronic symptoms, the colonies of cell wall deficient microbes multiply within the infected host cells and the host cells divide. Eventually the number of infected cells increase to another level of the pathogens life cycle and the host cells can split open and release pathogens that have the outer wall again which might increase risk of spreading the infection to other hosts.L-forms are referring to a “Life-form” stage of bacterial growth in which the bacterium can lose its outer wall and start growing within the interior of a human cell or other host cell. The following article by Amy Proal goes into extensive detail about the history of research in the field of autoimmune disease and cell wall deficient pathogens. http://bacteriality.com/2007/08/18/history/

Lida Mattman, a pioneer in the field of L-form microbes, is pictured at her microscope. She died at age 96 in 2008.  Obituary: http://www.lymenet.de/literatur/lida_mattman.htm

Sue Massie is a mother who found that Lyme’s disease was a problem for her husband, herself and their 6 children. She shares her family’s medical journey – they all were sick with low grade chronic symptoms. Dr. Mattman is quoted near the bottom of the article regarding the potential risk of infection from physical contact with a human carrier of Lyme’s disease (Borrellia burgdoferi):

“Dr. Mattman believes that touching can spread Lyme disease. The Lyme spirochete can actually occur in tears, and therefore can be transmitted to hands, which contaminates doorknobs, pens, people shaking hands, etc. This appears to be consistent with the observation that whole families often culture positive for Lyme and present with symptoms.” http://www.springboard4health.com/notebook/health_lyme_disease.html

  • A link to the book by Lida H. Mattman, Ph.D in Immunology from Yale University, “Cell Wall Deficient Forms: Stealth Bacteria“: http://www.lymebook.com/cell-wall-deficient-forms-mattman
  • A book review about Lida Mattman’s book, Cell Wall Deficient Forms: Stealth Bacteria:
    From Book News, Inc.
    Mattman (immunology, Nelson Medical Research Institute, Warren, MI) explores pleomorphic forms of bacteria and fungi, which are inconvenient to deal with but allow a much more precise identification of a pathogen and diagnosis of disease. She provides information to help researchers determine the organisms that should be added to the childhood vaccine, especially for boys; the bacterium found in its pleomorphic state in direct smears of synovial fluid of rheumatoid arthritis cases; the chronic disease for which an acid-fast organism is routinely found in smears of 72-h blood cultures in any routine medium; the bacterium that has a life cycle in the human erythrocyte as complex as that of Plasmodium malaria; the common pathogen of which the L form can permanently damage mammalian myocardium; and other microbes. No dates are noted for previous editions. Book News, Inc.®, Portland, OR http://www.personalconsult.com/articles/lymecellwalldeficiency.html
  • Excerpt from the book “The Top Ten Treatments for Lyme Disease” http://www.lymebook.com/marshall-protocol:  “In the past, sarcoidosis patients have received only minimal benefit from antibiotic therapy. But Dr. Marshall discovered that, upon reduction of 1,25-D levels, sarcoidosis patients can actually be cured with antibiotic therapy.”

Coinfections are a frequent problem within autoimmune disease sufferers. Sarcoidosis patients have had a variety of different species of pathogens cultured from blood samples. A weakness in immune strength may leave some people more susceptible to be a host for the types of pathogens that can survive in the L-form and colonize within human or other host cells. The good news is that the same treatment plan helps the human’s immune system to recognize the infected cells and reduce the infection without chemotherapy or other immune suppressing medications.

Benicar is a medication used in the Marshall Protocol, the treatment plan developed by Trevor Marshall, a biomedical engineer who worked on finding treatment for his own case of sarcoidosis.

Benicar acts to block the Angiotensin Receptor on cell surfaces. It may help the host defense by removing the disguise of “self” that the colonized cells may be using to confuse the healthy uninfected white blood cells. The overactivity of white blood cells is the characteristic response of autoimmunity that adds to long term degeneration. Previous medication strategies have been to suppress the overactive response. The use of Benicar every 6 hours maintains a constant inhibition of the Angiotensin Receptor that may help the healthy WBC identify the sick ones. Another benefit of Benicar therapy would be to reduce wasting of magnesium resources by the kidneys.

Excerpt from “The Stealth Pathogen Theory”  http://www.shoptown.com/Dean/ALS2Lyme.htm:

In the case of rheumatoid arthritis, Dr. Hoekstra has found that virtually all the patients he has studied have had significant amounts of a bacteria called Propioni bacterium acnes. “This is the genus and species of the organism we believe is responsible for propagating and perpetuating this disease,” says Dr. Hoekstra. “It is a very common bacteria in an altered state of being–it’s cell wall deficient.”

 The bacteria was first identified and described in 1981 by G.A. Denys at Wayne State University in Detroit, Michigan. “This bacteria is passed transplacentally, from mother to fetus, and this may be responsible for rheumatoid arthritis showing up in generations in a single family,” says Dr. Hoekstra.

 Why this bacteria is prevalent in seemingly all cases of rheumatoid arthritis is not clear; overuse of antibiotics may be a factor encouraging its growth. “The use of antibiotics is one of the most potent ways of inducing cell wall deficiency; bacteria seem to do this as a survival mechanism.”

 In other words, when a bacteria is transformed into a cell wall deficient form, it assumes different characteristics from the whole or native type of microorganism it used to be, Dr. Hoekstra explains. “The organism remains intact except it loses its cell wall and its antigenic characteristics, enabling it to function as a cellular chameleon.” When it loses its antigenic signature, the bacteria is able to mask itself against destruction by the immune system’s antibodies which can no longer recognize it as an antigen (foreign protein).

 Dr. Hoekstra’s mentor, Lida Holmes Mattman, Ph.D., also of Wayne State (now professor emeritus of biology), confirmed the causal role of P. acnes in a laboratory experiment. Dr. Mattman extracted the bacteria from the synovial fluid (which lubricates joints) of human arthritis patients, and injected it into chicken embryos. The chicks then exhibited symptoms of rheumatoid arthritis. When she treated the chicks with antibiotics known to disable P. acnes, the disease disappeared.

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.