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

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

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

Nrf2 Promoting Foods & Phytonutrients:

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

Nrf2 Promoting Foods and Phytonutrients

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References

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

Hypercoaguability; TNF alpha & Nrf2

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

Localized hyercoaguability & granulomatous sarcoidosis.

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

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

Calcium excess, magnesium deficiency and hypercoaguability.

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

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

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

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

TNF alpha and the NF-kB Pathway

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

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

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

Flavones are a type of Flavonoid

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

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

Onions and Green Tea – ECGC

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

Orange Zest – Tangeritin

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

Vinpocetine

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

Long term steroid use may also increase coagulation risk.

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

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

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

Dehydration

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

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

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

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

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

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

Take Home Points

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

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

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

References

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Why should we care about demyelination?

This post is a summary of two recent posts:

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

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 (22) or 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. (22) Myelin 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./  

Pomegranate extract – Master Chef Challenge update

For anyone following along with the pomegranate peel experiments  (previous post)- update, I had a lot of pomegranate extract thawed at the same time and for a dietitian that means reheat to steaming to assure food safety. So it was an opportunity to experiment some more with trying to adjust the acidity again. When baking soda is added to a hot acidic liquid there is an obvious bubbling reaction and change in color of the liquid. I have pH strips to check acidity and did manage to adjust the acidity of the extract. The taste is still not great but chronic illness and mood issues are not great either. After three cups of experimental attempts my mood is awesome *(see additional note) and I have some recipe details:

6 cups of pomegranate extract  (previous post)

2 Tablespoons Cardamom powdered spice

1 teaspoon Gumbo File powdered spice (Sassafras Leaves, powdered and used in Gumbo’s in Creole style cooking)

1 teaspoon Baking Powder

  1. Add the Cardamom and Gumbo File to the Pomegranate Extract and stir well to break apart any dry lumps of the powdered spices. The Gumbo File acts as an emulsifier and is a digestive aid and the Cardamom adds flavor, phytonutrients and would help alkalize the mixture in addition to the alkalizing power of the Baking Soda.
  2. Bring the mixture to a boil.
  3. Add the Baking Soda and stir. Remove the mixture from the heat and keep stirring. It will froth up and stirring helps keep it from frothing over the top of the pan. The color changes from pinkish to brown from the Cardamom spice.
  4. To drink as a beverage dilute with equal parts water to Pomegranate Extract.

This would be an acquired taste – aka “not good” until you get used to it, or not good at all but the mood and health benefits are worth for me at least. It is also a diuretic which means it is like beer or coffee in the way it increases kidney activity and urine production so it is best to have it earlier in the day followed by plenty of glasses of water early in the day so that you aren’t waking up in the middle of the night as much. Overly acidic, dehydrated body fluids can increase work for the kidneys and result in a frequent feeling of needing to go urgently but then not producing much quantity – drink plenty of water early  in the day and produce plenty of dilute quantity early in the day and a diuretic can help cleanse toxins from the body instead of being a middle of the night problem.

Since pomegranate growing season is limited the powdered spice made from Sumac might be a health substitute. It has been shown to have a range of health benefits, and is also a diuretic. Its phytonutrients are similarly colored suggesting there might be some similar antioxidant content as well. The gallotannin group of phytonutrients are in common and would likely promote Nrf2. (More about Sumac in this post) (a series of posts on Nrf2)

To put a financial perspective on this – for my health needs the pomegranate extract or pomegranate seeds and cardamom powder and a few other good sources of phospholipids are adequate replacements for my medical marijuana which cost me around $1000-1200 per month. The medical effects are slightly different and not quite as good for pain killing properties but the negative psychological effects that can occur with withdrawal for some people are also not present.

To review – cannabinoids are a group of chemicals that are made within the cells of most species and are similar to the group of cannabinoids found in the cannabis plants commonly known as marijuana or hemp. Medical marijuana has a euphoria producing one known by the chemical initials THC while hemp has only non-euphoria producing cannabinoids. Both types can have medical or other basic health benefits. Cannabinoids are found throughout membranes and add to cell wall flexibility and help with messenger chemical type activities that can help reduce inflammation and fight infection. Some people such as myself can have genetic differences that make it impossible to make the chemicals internally as in average health. I have had minor health problems since infancy and having external dietary sources of phospholipids or cannabinoids helps my body and mood and immune system. More information about the topic is available in the post/article Is it Addiction or Starvation?

People with problems with binge eating disorders, alcohol abuse tendencies, meth or heroin/opioid abuse tendencies, or seem to have an excess use of marijuana, and nicotine to a lesser extent all may actually have underlying genetic differences that leave them in need of increased dietary sources of phospholipids/cannabinoids. The article Is It Addiction or Starvation? has some legal food sources in addition to pomegranate seeds and cardamom spice. It doesn’t mention the Middle Eastern spice Sumac but it might help also.

*Additional note – three cups was likely to large of a serving, an awesome mood for someone with unstable mood issues was too much of a good thing – Newton’s Law of Gravity may apply metaphorically, “What goes up must come down.” I had a worse mood problem later in the evening. Today (the next morning) I’ve enjoyed a few spoonfuls of the spicy, creamy slightly thickened mixture in my coffee and it is good to my “acquired taste.” The thing about having acquired an acquired taste for something is that you then want to acquire more – pun intended.  The pomegranate season in Australia turns out to also be November to March so that isn’t much help. Processing pomegranate peel during the growing season would be necessary if I hope to continue to be able to acquire pomegranate extract all year long. It has medicinal benefits according to the research that is available, (see links in earlier posts on this site).

New Zealand isn’t ideal for pomegranate either as the summer length may be too short some years, however their harvest season is February-April: “Pomegranates grow best in areas with cold Winters and long hot, dry Summers.” (Pomegranate Wonderful)

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.