Localized hypercoaguability & Sarcoidosis; TNF alpha & Nrf2

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)

*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 .

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)

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.
  • 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.

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Pomegranate extract update – has similar mechanism to NSAIDs

Update, 8/18/2018, for anyone interested in phytonutrient biochemistry or herbal medicinal foods: Wintergreen and wintergreen berries are also a natural source of a painkiller in the NSAID group – aspirin. The plant can also be a source of phytonutrients that activate TRPA1 channels which can affect fluid balance and other symptoms. Winterberries are in the cranberry family and have a minty flavor. They are in season currently and eating more of them seems to increase my symptoms of inflammation and swelling more than the pomegranate extract or pomegranate seeds. Having too many variables in an experiment makes it unclear which factor might be a cause or if both may be involved. Experimental method tries to narrow variables to one factor at a time. Stopping both pomegranate products and wintergreen berries helped but other symptoms got worse, adding pomegranate back to my diet didn’t make the inflammation/swelling symptoms much different but more recently adding the wintergreen berries back into my diet did make the symptoms of lower leg inflammation/swelling and pain worse.

An excerpt from one of my other websites, G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

  • “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73) (effectivecare.info, G3)

My ongoing self study of pomegranate extract for my mental and physical health symptoms has led me to use a fairly small dose, daily though is still best. Missing even a few days seems to increase mood and anxiety problems but using a very large serving has some side effects. Lower leg and foot swelling is associated with some physical health problems but it can also be a side effect of NSAIDs pain killers such as ibuprofen. (7) Pomegranate extract has been shown to reduce pain and inflammation by the same mechanism as NSAIDS – inhibition of cyclooxygenase enzymes (COX1 and COX2,  with more inhibition of COX2 than COX1). It also may have an anti-inflammatory effect by reducing inflammatory cytokines that signal increase in production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2). (1) Prostaglandin E2 is made from arachidonic acid and is involved in the inflammation associated with rheumatoid arthritis and osteoarthritis. (2) Nitric oxide can be beneficial but it can also transform into reactive oxidative species and add to the antioxidant burden of metabolism. (5) (9) Other studies including an animal study on obesity found pomegranate extract reduced inflammatory biomarkers and increased nitric oxide, which might make it helpful for Metabolic Syndrome. (6)

Pomegranate extract was found helpful in a dose related level against mammary tumerogenesis in an animal study, (0.2-5 gram/Kg body weight was used). Reducing COX2, heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) pathways, and increasing Nrf2 pathways were found to be part of the mechanism for benefit. (4) That amount could be quite a lot. Equivalent amounts for a 75 kilogram/165 pound human would be 15-375 grams per day or roughly one tablespoon (15 grams approximately)-13.4 ounces/27 tablespoons per day. (Mammary tumerogenesis means the initial onset of breast cancer tumors.)

It helps to prop my feet when sitting or even lay down with my feet above my heart. I’m getting better at typing while laying down. Better mood and having feeling in my fingertips is worth it. There may some other health or diet issues affecting the leg swelling. Heart or kidney or vein problems can be a cause. (7) I do have vein problems and may have heart issues, which can be an increased risk with hyperthyroidism. Cutting back on salt, daily exercise, and elevating the lower legs above the level of the heart several times per day for a half an hour is recommended, wearing compression socks is also a recommendation and that makes me feel old. (7) Maybe 52 is old.

Lymphedema – lower leg swelling due to reduced drainage from vein problems may be the best fit for my personal history, and lack of stretching exercises lately may be part of the reason the problem has become worse lately. Physical therapists explain the problem and provide exercise, massage and compression wrapping suggestions in a free video available online. (8) The exercise routine is similar to what I generally do when I do stretching exercises – so that seems like a good habit to return to my daily schedule.

Lower leg swelling has been a symptom for me at various stages of previous ill health and with some other medications I’ve used in the past, but currently it does seem worse when I use larger amounts of the pomegranate extract. One teaspoon a day helps with the stable mood and I haven’t had numbness in my fingertips in months with the ongoing daily use of pomegranate extract in larger amounts, 2-3 tablespoons was typical. I stopped use of it altogether when the leg swelling became a problem to see if the swelling would get better but the mood symptoms got worse again after having seemed fine for quite a while – quite a while while using pomegranate extract daily and the leg swelling didn’t get a lot better. Being not well is unpleasant and some side effects can be better than being unwell.

Breast cancer treatments currently may cause hair loss, severe vomiting and may leave the patient with cognitive decline afterwards, and pomegranate extract doesn’t cause any of those symptoms in the amounts that I’ve tried. It is a diuretic and causes increased urination which I cope with by drinking extra fluids and using the pomegranate extract early in the day rather than at night. I may be preventing breast cancer tumor development (4) while drinking extra fluid and urinating in increased amounts – getting old isn’t great but the alternative isn’t better. I may go buy my first pair of compression socks and feel young at heart if not in body.

Industry math – one pomegranate peel makes about six cups of extract by my method which would provide 288 teaspoons/96 tablespoons. It may have improved somewhat but the worsening in mood was more obvious.  From an industry perspective getting 288 servings of a mood and nerve treatment from one pomegranate peel seems like it could be profitable. Dehydrating one teaspoon into a capsule serving also seems possible. Side effects with psychiatric medications are unfortunately common and can include swelling/edema of the lower legs or more severe edema including facial edema.

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

  1. Shukla, Meenakshi & Gupta, Kalpana & Rasheed, Zafar & A Khan, Khursheed & Haqqi, Tariq. (2008). Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX-II activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro. Journal of inflammation (London, England). 5. 9. 10.1186/1476-9255-5-9.
  2. Jean Y. Park, Michael H. Pillinger, Steven B. Abramson, Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases, Clinical Immunology, Vol 119, Iss 3, 2006, pp 229-240, ISSN 1521-6616, https://doi.org/10.1016/j.clim.2006.01.016.
    https://www.sciencedirect.com/science/article/pii/S1521661606000453 (2)
  3. Arachidonic Acid – an overview, ScienceDirect, https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid (3)
  4. Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling PathwaysNutrients. 2017;9(5):436. doi:10.3390/nu9050436. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452166/ (4) From Abstract: “Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis.” From Introduction:”During the last decade, pomegranate fruit has been gaining a widespread reputation as a dietary supplement as well as a functional food due to emerging scientific evidence on potential health benefits, including prevention and/or treatment of cardiovascular ailments, neurological disorders, oncologic diseases, dental problems, inflammation, ulcer, arthritis, microbial infection, obesity, diabetes, acquired immune deficiency syndrome and erectile dysfunction [,,,,,]. Pomegranate fruit contains phytochemicals, including flavonoids (e.g., anthocyanins and catechins), flavonols (e.g., kaempferol and quercetin), flavones (e.g., apigenin and luteolin), conjugated fatty acids, hydrolyzable tannins and related compounds which are thought to be responsible for various biological and pharmacological activities [,,,,,]. Based on preclinical and clinical studies conducted by various laboratories worldwide, pomegranate-derived substances, such as juice, extracts and phytoconstituents exhibited cancer preventive and therapeutic effects against colon, liver, lung, prostate and skin cancer [,,,,]. Various extracts, fractions and phytochemicals from pomegranate fruit, peel, seed and flower demonstrated cytotoxic, antiproliferative, proapoptotic, antiangiogenic, anti-invasive, and antimetastatic properties against estrogen receptor-positive and ‑negative breast cancer cells [,,,,,,,,,,,,,]” (4)
  5. Matsubara K, Higaki T, Matsubara Y, Nawa A. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia. Miller FJ, ed. International Journal of Molecular Sciences. 2015;16(3):4600-4614. doi:10.3390/ijms16034600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394437/ (5)
  6. Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P. D’Armiento, Carmela Fiorito, Louis J. Ignarro, Claudio Napoli,
    The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats, Nitric Oxide, Volume 17, Issue 1, 2007, pp 50-54, ISSN 1089-8603, https://doi.org/10.1016/j.niox.2007.04.005.
    (http://www.sciencedirect.com/science/article/pii/S1089860307000432) (6)
  7. Swollen Legs: Causes and Treatments, WebMD, https://www.webmd.com/dvt/why-legs-puffy#1 (7)
  8. Bob Schrupp, Brad Heineck, 10 Exercises for Leg Lymphedema (Swelling or Edema of the Lower Extremities). physicaltherapyvideo, https://www.youtube.com/watch?v=3t8Kp99e50k&feature=youtu.be (8)

  9. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. International Journal of Molecular Sciences. 2018;19(5):1496. doi:10.3390/ijms19051496.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983711/ (9)

Why care about demyelination?

We need to care about demyelination as a society because it may be a factor underlying many conditions that have been occurring at increasing rates. The high cost of health care is not just due to the cost of individual medications or the price of hospitalization but is due to the additive cost of increased numbers of individuals needing care. Autism care alone is estimated to likely reach $500 billion by 2025 for care in the U.S. alone, (link), demyelination or disordered myelin formation is thought to be involved. Our food supply may provide calories but it may no longer be supporting health due to imbalance in some nutrients and lack of sufficient amounts of other nutrients – in addition to personal choices for some people leaning toward convenient and tasty foods that provide very few nutrients besides calories.

The other reason to care about demyelination as a society is because the early symptoms can occur for years without clear reasons and may disrupt relationships or the ability to hold a job – personality changes including anxiety and anger, paranoia and a short temper – problems with impulse control and the ability to follow through on planned actions or with communication and the ability to tell the truth instead of substituting other statements that may seem illogical and obviously far from the truth. Problems with impulse control and a tendency toward mood problems may also include an increased risk for suicide or self injury or violence towards others.

The medical research is complex and I haven’t seen all the loose threads together yet, so I will summarize my summary points in a more concise list here and am working on a more organized document elsewhere. This list combines my tips from the previous post with the work of the other summary article (22) — I was also given the link to another summary article which also has tips which I have not incorporated here. It provides an excellent overview about myelin production and function –selfhacked/myelin – what I and the authors of (22) and {selfhacked} have in common is that we all got sick and sought information about regaining our health for ourselves and are sharing the information in case it might help others.

My personal goal is to not become paralyzed (post: ALS & CBD receptors), number of clicks on a website is not something I pay attention to. The loose threads that I’ve woven together in this series of posts which are not included in the excellent selfhacked article are that a) many of the herbs or phytonutrients found helpful for myelin regeneration are Nrf2 promoting which is also important for myelin regeneration and/or reducing oxidative stress that may lead to more degeneration of myelin. b) Foods that are good for promoting Nrf2 often are also good sources of cannabinoids or phospholipids which can be protective. c) And preventing excessive cell death or excess intracellular calcium may decrease the excess production of cytokines by decreasing release of cannabinoids from cell membrane storage and their breakdown into arachidonic acid and eventual transformation into cytokines and other inflammatory chemicals.}: 

Strategies to help prevent the breakdown of myelin or help promote regeneration of myelin:

{In the past at different points in time, I personally have experienced and improved with supplementation or diet changes physical and mental symptoms of vitamin B1, B5, B6, folate and B12 deficiencies; iodine, magnesium, calcium and zinc deficiencies; vitamin/hormone D and calcium excess at a different stage of health;  cannabinoid/phospholipid deficiency; inadequate protein and general malnutrition due to the zinc deficiency which can greatly reduce appetite at one stage and due to severe bowel mal-absorption more recently; omega 3 fatty acid/omega 6 fatty acid imbalance; and also lack of sleep/melatonin and lack of oxygen/excess toxins in the air; health requires all of the nutrients and adequate oxygen, exercise, sleep and stress coping.}

  1. Vitamin B1, thiamin deficiency, chronic, severe – Wernicke’s encephalopathy may be more of a risk for severe alcoholics and people with anorexia – severe lack of appetite or the eating disorder anorexia nervosa.
  2. Vitamin B12 deficiency – may be more of a risk for people with low stomach acidity, due to older age or chronic use of calcium type antacids; or due to genetic reasons limiting production of Intrinsic Factor; or due to a vegan diet without supplementation of vitamin B12 or inclusion of Nutritional yeast flakes in the diet.
  3. Zinc deficiency (22or copper  excess (link).
  4. Adequate but not excessive lithium may increase myelin production. (22)
  5. Adequate but not excessive iron intake is needed for production of myelin.
  6. Magnesium deficiency or poor intestinal absorption of magnesium, or lack of adequate protein and phospholipids in the diet for the body to be able to store magnesium in the normal manner within the intracellular fluid.
  7. Inadequate calcium or vitamin D can be a factor but excessive intake of either can also be a factor in cell breakdown and risk of demyelination. If taking vitamin D as a supplement the vitamin D3 form may be most bioactive and taking vitamin K2 with it may help with myelin production (22) and protect against osteoporosis. Green leafy vegetables are good sources of vitamin K.
  8. Adequate intake of cholesterol is needed as a building block for our own production of vitamin D and other steroid hormones and as a building block for myelin. (22) Pregnenolone is a steroid hormone precursor that may benefit some people when used as a supplement. It and other steroid hormones are involved in signaling increased production of myelin. Testosterone insufficiency may also negatively affect myelin production. (22)
  9. Excessive intake of free glutamate or aspartate – excitatory amino acids that are commonly used as flavoring or sweetening agents in foods or may occur naturally in fermented foods or alcoholic beverages.
  10. Adequate protein is needed to support a variety of body functions in addition to supporting magnesium levels. Uridine is a nucleotide base (part of DNA that is a combination of a type of sugar and an amino acid) that is also is involved in energy metabolism, fasting occasionally may increase our own production (more info). Insufficient amounts may negatively affect myelin production and use as a supplement may help some people. (22)
  11. Insufficient calories to provide the body enough glucose to support mitochondrial health. They can use protein or fats for energy but it shifts the metabolism more towards oxidative stress.
  12. Occasional fasting and/or a low carbohydrate diet may help promote autophagy due to increased use of ketones for energy (22) but may cause health problems due to excess oxidative stress or an increased burden of nitrogen waste removal for the kidneys when followed long term.
  13. Lack of antioxidants due to lack of Nrf2 within the body to promote our own production of antioxidants internally; and/or lack of antioxidants within the diet, including vitamin C, (22), would decrease our ability to detoxify the reactive oxidative chemicals produced during normal metabolism or which are produced at increased rates when protein or fats are being used for energy instead of glucose.
  14. Use of the herb ashwagandha or Gingko biloba (22) may help protect against oxidative stress and protect against demyelination by promoting Nrf2. (ashwagandha & Nrf2) (an overview of Nrf2 metabolism, its potential benefits for conditions such as Multiple sclerosis, and Gingko biloba and pomegranate are mentioned as promoters of Nrf2: nutricology/newsletter, see first article) (other Nrf2 promoting phytonutrients/foods and menu ideas: G10: Nrf2 Promoting Foods.) Flavonoids are one of the groups of phytonutrients that helps promote Nrf2; and also may help protect myelin production. (22) Medicinal mushrooms, including Hericium Erinaceus, Lion’s Mane Mushroom,(22), may also help protect myelin production and prevent breakdown by reducing oxidative stress (link) and promoting Nrf2. (link)
  15. Having a healthy balance of omega 3 fatty acids and omega 6 fatty acids in the diet helps reduce risk of inflammation/oxidative stress and also helps us build healthy membranes which are necessary to control flow of minerals and other chemicals from the exterior to interior of cells and organelles such as the mitochondria.
  16. Inadequate iodine for healthy thyroid hormone production, (22); may be a combined problem of excess presence of bromide, fluoride and perchlorate in the diet or environment.
  17. Lack of oxygen due to poor air quality, or smoking, or health problems causing inadequate breathing function. Emotional or physical stress may also increase the need for oxygen or increase the tendency to hold our breath; Take ten deep breaths and think before you speak is good advice for any emotionally stressful situation because oxygen is needed to think rationally and we tend to hold our breath when we are upset.
  18. Avoid extreme physical and emotional stress.
  19. Avoid toxins.
  20. Get adequate sleep at night, and a brief nap during the day may be beneficial for some people. Melatonin helps promote myelin production and inadequate sleep and having lights on at night can disrupt our production of melatonin. (22)
  21. Adequate exercise (22) and stretching regularly helps move nutrients throughout the body and remove toxins in the lymphatic fluid for further detoxification and eventual removal from the body.
  22. Wear a helmet for any activity that may cause head trauma and avoid sports which may cause frequent closed head trauma and especially when helmets are not used (sorry soccer, football, hockey, (link), and boxing fans).
  23. Adequate phospholipid and other phosphonutrients or cannabinoids may be necessary to include from external sources if genetic differences or other health problems or age interferes with the body’s internal production capability. Dark cocoa products, cardamom powder, pomegranate and pumpkin seeds are a few legal dietary sources.
  24. Use of ibuprofen and/or ginger (approximately 1/2 teaspoon per day) may help prevent breakdown of our body’s supply of cannabinoids, breakdown of which may then lead to increased breakdown of cells and may then lead to increased degeneration of myelin.
  25. Lack of any B vitamins or genetic differences in the ability to remethylate folate and vitamin B12 may disrupt the ability of mitochondria to generate usable energy from glucose or proteins and fats, and may reduce production of myelin. (22) Inositol and choline may be particularly important for myelin production. They are considered to be in the B vitamin group but was discovered more recently than the numbered series of B vitamins. (22)
  26. Low Level Laser Therapy – I am not familiar with this, see #10: (22), but I have read elsewhere that certain types of light can stimulate activity levels. (Haier)
  27. Practice, practice, practice – new things. (22Myelin is produced in response to learning [45] so remaining mentally stimulated with new experiences and learning new topics or techniques keeps signalling the body to produce myelin. 
  28. Brain-derived Neurotrophic Factor, (BDNF), the brain’s growth factor, may help increase production of myelin by increasing production of brain cells, which include oligodendrocytes. (22) Ways to promote BDNF (link, from within 22) fortunately overlap with the strategies for protecting against demyelination already mentioned above or included in the list of Nrf2 promoting foods.
  29. Reducing exposure to electromagnetic fields (EMF) – energy leakage from laptops, smartphones, WiFi, televisions, and other strong sources of electicity may help protect against myelin degeneration. (22)

References and more details for some of this information were included in the last two posts:

  • Good News/Bad News about Multiple sclerosis Research (7/26/2018)
  • Demyelination, continued. (7/28/2018)

/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./