Pomegranate peel may be the best part – medicinally

I’ve been experimenting with making pomegranate peel extract and it may be the best part medicinally but is quite acidic and quite bitter. Mary Poppins sang that a spoonful of sugar helped the medicine go down and she is on to something. Medicinal herbs may be the bitter ones.  Sugar does help with the taste, but excess amounts of it can help worsen inflammation, so just a spoonful is important. Diluting with extra water and adding a concentrated fruit juice also helped with flavor.

I’m taking notes but am still in the testing phase so this is a summary – yes it seems possible to make an extract from the peel and inner membrane part of the pomegranate. The taste is something that a sick person would tolerate because feeling better is worth a lot including drinking something not very good as quickly as possible. However the healthy person is still likely to prefer the pomegranate juice or juicy crunch of the seeds. If there are seasonal issues one simple experiment worked well – the juicy seeds freeze quite nicely so making a large batch of peel and membrane extract could include simply freezing the seeds for later use in salads or as a sweet and tangy treat. The juice is also tart but the peel extract I made was more acidic than coffee I added baking soda to make it less acidic and easier for the digestive system to tolerate.

The extract did help more of my symptoms than the seeds do. I’ve had early signs of finger numbness, possibly Raynaud’s Disease/Syndrome, which doesn’t really have any treatments. The extract helped restore feeling to my fingers but it was temporary, just that day so the larger quantity of the treatment mentioned in the last post on this topic which used 1 – 10 grams/kilogram for 8 weeks for hepatocellular carcinoma might be best spread out through the day for someone with a more severe illness. Half a cup per day for someone less ill and a half a cup every three to four hours throughout the hours spent awake for someone who is more severely ill might be what helps symptoms. If every cell of the body needs the substances, every hour of the twenty-four, then one dose one time per day might leave the body under-treated for most of the 24 hours and only relieve symptoms for a few hours.

Raynaud’s Syndrome/Disease is referred to by both names. It was mentioned in the search engine results but the article is only available as an Abstract which doesn’t mention any specific conditions: (1). The condition is discussed in an full text available article on oxidative stress and Nrf2. It mentions green tea extracts and Gingko biloba as possibly helping reduce oxidative stress: Review Article: Oxidative Damage and Antioxidative Therapy in Systemic Sclerosis,   (2).

Gingko biloba is also mentioned along with Raynaud’s Disease in this article. A standard dosage is mentioned as being used once or twice per day: “The standard clinical dose of EGb 761 is 120 mg (~1.7 mg/kg) once or twice daily;” Egb is a standardized formulation that contains a certain amount of the active phytonutrients of the Gingko biloba herb which are called gingkolides. It is a traditional herb that was used in cooking and as a medicine in Chinese and Japanese history for conditions such as asthma or as a cough medicine. In the discussion of Future Directions for research the authors suggest more study of dosing as the amount used in preclinical trials was significantly more than used in many clinical trials, “(100 mg/kg compared to <2 mg/kg, respectively),” although some used a larger dose, (300 mg daily).  (3).

I do take a capsule of Gingko biloba daily but not the Egb formulation. The dose I have been using is 60 mg standardized to include “24% Gingko Flavoglycosides = 14.4 mg and 6% Terpene Lactones = 3.6 mg” – which suggests it is a fairly low dose compared to some of the research studies that used 100-300 mg of the Egb formulation. (3)The Egb formulation also includes flavanoids which include one that has been found to help increase Nrf2:

“Beyond oxidant scavenging, the flavonoid isorhamnetin was able to upregulate antioxidant enzymes through Nrf2 activation.(3).

Take home point – clinical trials are a lot of work and accurate dosing, both amount used, concentration of the active phytonutrients, and frequency the dose is used throughout the day, and how large the patient is, are all important factors for effectiveness of the herbal preparation at relieving symptoms of a disease or preventing chronic illness.

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.

  1. DaigoSumiAikoManjiYasuhiroShinkaiTakashiToyamaYoshitoKumagai., Activation of the Nrf2 pathway, but decreased γ-glutamylcysteine synthetase heavy subunit chain levels and caspase-3-dependent apoptosis during exposure of primary mouse hepatocytes to diphenylarsinic acid., Toxicology and Applied Pharmacology, Vol. 223Issue 3, 15 September 2007, Pages 218-224.    http://www.sciencedirect.com/science/article/pii/S0041008X07002633 (1)
  2. Bogna Grygiel-Górniak and Mariusz Puszczewicz,Review Article: Oxidative Damage and Antioxidative Therapy in Systemic Sclerosis, Mediators of Inflammation, vol 2014 (2014), Article ID 389582, 11 pages. https://www.hindawi.com/journals/mi/2014/389582/. (2)
  3. Kevin M. Nash and Zahoor A. Shah., Current Perspectives on the Beneficial Role of Ginkgo biloba in Neurological and Cerebrovascular Disorders., Integr Med Insights. 2015; 10: 1–9.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640423/ (3)

The idea of taking one capsule of ‘Nrf2 Activator’ seems unrealistic – to me

This is a continuation of the last post which expanded on a topic brought up in the previous post. Nrf2 is an important chemical produced within the body when hormone D is available to turn on the gene that encodes Nrf2 and then Nrf2 can activate many other genes which are the map/encode/are the recipe card for proteins which are our own natural antioxidants and which are important for detoxifying the oxidative stress free radicals which are a natural part of energy production – turning glucose/blood sugar into usable energy.

The idea of taking one capsule of an ‘Nrf2 Activator’ seems great and might seem like a natural idea to our medicine mindset, however medicine and food are different. Medicines that can be taken in one pill per day tend to be something that triggers other events and which might not be needed within every single cell. Food on the other hand is needed in every single cell, like if every cell were its own Taxi cab in need of gasoline and motor oil and radiator fluid and windshield wiper fluid and whatever other things go on within a motor vehicle – we just think about the gasoline because it is needed most often but the car also needs those other fluids which can be reused for awhile. Medicine in a single pill per day type is more like the windshield wiper fluid or motor oil – it lasts awhile but eventually runs out or becomes less efficient.

A brief glance at the list of phytonutrients and foods that help promote production of Nrf2 suggests that since it is needed in every single cell of the body – as energy production and free radical production take place in every single cell – that it needs to be produced in a larger quantity and more regularly throughout the day then any one capsule might be able to promote/activate.

Magic bullet/one pill a day medications are not the same as the essential building blocks of the bulk macronutrients, protein, fats, and carbohydrates; or even the same as the trace micronutrients, the vitamins, minerals, phospholipids and essential amino acids, fatty acids and essential sugars/starches (specialized types of carbohydrates), which are needed in smaller amounts then the bulk supply of protein, carbohydrates and fats. Improving intake of any one group is going to help health but to really help improve health all the groups, macro and micronutrients, are needed on a regular basis. Some can be stored longer than a day or two because they are fat soluble and are stored within cell membranes and other fat storage areas of the body but even those run out eventually. Vitamin D is a trace nutrient that can be made within our bodies during sun exposure if adequate cholesterol is available (it is a slight chemical modification of the cholesterol molecule) and supplies that are made during summertime in areas with seasonal changes can last throughout most of the winter but tend to start running out during early spring/late winter.

Skipping ahead a bit – I have several of the chronic conditions that were listed in the last post and I have several genetic differences from average that may be making it more likely for me to have difficulties producing some of the important factors involved in detoxifying oxidative stress chemicals. I have managed to change my diet enough to feel better and to have the chronic conditions be considered ‘in remission’ but I know that it has to do with my daily habits in diet and in the supplements that I’ve added to my daily routine. When I get forgetful or too stressed to remember the supplements or start eating fewer of the healthy foods I’ve added my symptoms can start returning very quickly. So the idea of taking one capsule of ‘Nrf2 Activator’ per day seems like a nice but very unrealistic idea. Every cell of the body produces free radicals all day long, they need antioxidants all day long, which means they need Nrf2 helping promote production of our own natural antioxidants – all day long.

I’ll get back to the menu and recipe ideas shortly but first a list of the supplements I take  – the herbal supplements can vary somewhat from month to month as they may all be beneficial but they all cost some money but they don’t cost as much as expensive hospital bills or expensive pharmaceuticals (chemotherapy for cancer can cost a quarter of a million dollars). I have to avoid some nutrients as my genetic condition leaves me at risk of excess for some things and my autoimmune hyperthyroid condition is made worse by too much iodine intake so I take some B vitamins and trace minerals as individual supplements everyday but I’m only going to list the herbal supplements here. They may be beneficial because they are likely to have some of the list of phytonutrients mentioned as promoting Nrf2 in the last post. I’m sharing this list not as a recommendation but as an example of what I find helpful to help keep my own autoimmune, chronic inflammatory bowel, migraine, chronic pain and itch problems mostly in remission and help with mood stability as I’ve been diagnosed with bipolar disorder in the last few years – it can be made worse by menopause or may be menopause, I’m hoping to get more stable moods as I move further through ‘the change.’

-I try to get only supplements with vegetarian gelatin or gelatin free and free of modified food starch as those ingredients may make my health worse – in alphabetical order for ease of reference:

  1. Artemisinin – 200 mg, I just added this one, I’m not sure if I will continue it past the first bottles that I ordered.
  2. Astragalus – 500 mg – this is also a recent addition.
  3. Black Cohosh – 300 mg – this is for menopausal female support.
  4. Dong Quai – 1.13 grams – also for menopausal female support.
  5. A mixture for menopause support which contains Maca extract, Angelica gigas, Pholomis umbrosa, Cynanchum wilfordii, and Cordyceps extract (a beneficial mushroom). – 1590 mg total for the mixture. This is a recent addition but I’ve found the Black Cohosh and Dong Quai helpful for a few years.
  6. While on the area of menopause support I also have used a topical Wild Yam Extract cream for a natural source of progesterone. I’m better with it then without. Menopause for women starts as peri-menopause and the process can last more than a decade.
  7. Gingko Bilobo – 60 mg. I’ve taken this off and on for many years. It may be helpful for mental sharpness/brain vascular system. My migraines may have to do with blood vessel problems.
  8. Kava Root – 800 mg – I have taken this for a few months as it may help promote more stable mood and my mood swings were quite bad for a while.
  9. Milk Thistle – 1260 mg/ 240 mg active phytonutrients – This may help with liver health and I added when reading about the importance of the liver for basically everything else in the body. I’ve only been taking it for a few months/ half a year.
  10. Oil of Oregano – 60 mg – I eat Italian Seasoning in teaspoon quantities on my salads, it is an herb mix containing oregano however the health benefits are suggested to be beneficial for general health and the oil is a more concentrated source. Eating larger quantities of oregano would be very strong flavor. I’ve been taking the concentrated oil for at least a half a year or more, it seems helpful. It is difficult to really know if something helps – it is easier to tell once you run out of something and don’t replace it if you start feeling a little worse again.
  11. Resveratrol – 250 mg, with Quercetin – 150 mg – I’ve taken both of these off and on for many years. They are both antioxidants that may help with skin health and general well being is a good general term.
  12. Slippery Elm Powder – 400 mg – I’ve taken this off and on over the years whenever I have a bad cold with a sore throat as it was in a soothing tea. The herb provides a mucilaginous protective coating to the digestive lining. More recently I added it about a year ago when my digestive problems began – it’s my go to herb for gastrointestinal tract problems. Marshmallow Root powder would act similarly. I have recently also been having a Tablespoon of Chia seeds in water everyday as they also help the GI tract in a similar way. Water soluble fiber is another term for mucilaginous substances.

So taking one bottle with one capsule per day of an Nrf2 Activator sounds like a nice idea for a pharmaceutical representative but not for dietitian recommendation.

The list of phytonutrients, for convenience:

Specific foods or phytochemicals mentioned to help increase Nrf2 include:

  • sulforaphane from cruciferous vegetables, (such as broccoli and cauliflower);
  • foods high in phenolic antioxidants, (This is a large group including bright yellow and red fruits and vegetables, and deep purple produce. The group includes the subgroup flavonoids which include anthocyanins, flavonols, and it also includes the less familiar subgroup chalcones which are found in the commonly used fruits apples, pears and strawberries. The group also includes aldehydes which are found in vanilla and cinnamon, phenolic acids which include salicyclic acid, and tannins which are found in tea, coffee and wine. Baking cocoa and cherries, beans and whole grains are also mentioned, the summary point would be eat more fruits and vegetables; see: (11))
  • the long-chained omega-3 fats DHA and EPA, (salmon, tuna, sardines, krill oil, ground flax meal, walnuts, hemp seed kernels);
  • carotenoids (especially lycopene), (such as carrots, winter squash, sweet potatoes, cantaloupe, apricots, and lycopene is in tomato, watermelon, pink grapefruit, guava); 
  • sulfur compounds from allum vegetables, (such as onions, garlic, shallots, green onions); 
  • isothiocyanates from the cabbage group and
  • terpenoid-rich foods. (Terpenes are found in real lemon and lime oil, rosemary, oregano, basil and other aromatic green herbs).
  • The Mediterranean and the traditional Okinawan Diets are also mentioned as being Nrf2 promoting diets. See: (1)

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.

 

Nrf2 – helps activate beneficial genes, protective against inflammatory conditions

Nrf2 is an acronym for a substance that helps activate genes that protect against oxidative stress and the resulting inflammation from excess oxidative chemicals. Nrf2 is a lot easier to remember then: nuclear factor erythroid-2-related factor 2 (Nrf2). 

The list of chronic illnesses and genetic conditions that it may help prevent or treat is also quite long. The protective benefits against electromagnetic field radiation that was discussed in the last post may be due to the genes activation and resulting increased protection against oxidative stress chemicals – and this mechanism may be the same pathway for its beneficial role in preventing or treating the long list chronic illnesses.

It has been studied by a number of different groups in the prevention or treatment of: 

  • Cardiovascular diseases including atherosclerosis, ischemic cardiovascular disease, vascular
    endothelial dysfunction, and heart failure;
  • Neurodegenerative diseases including Alzheimer’s, Parkinson’s, ALS, Huntington’s diseases;
  • Cancer (prevention);
  • Chronic kidney diseases;
  • Metabolic diseases: Type 2 diabetes; metabolic syndrome; obesity;
  • Several types of toxic liver disease; (not from the pdf article (1) – Nrf2 helps the liver to better utilize free fatty acids and triglycerides as an alternate energy source during times of starvation/malnutrition, which speculatively then, a deficiency of Nrf2 might be a factor in fatty liver disease (8))
  • Chronic lung diseases including emphysema, asthma, and pulmonary fibrosis;
  • Sepsis;  — (sepsis is a serious type of infection that spreads throughout the blood system.)
  • Autoimmune diseases;
  • Inflammatory bowel disease;
  • HIV/AIDS;
  • Multiple sclerosis;
  • Epilepsy;
  • See Table 1 for the list of studies regarding Nrf2 and the above conditions: (1).

Other diseases or conditions that may also be helped by adequate levels of Nrf2 have been less well studied but the same mechanism of reducing oxidative stress might also benefit in the prevention or treatment of:

  • “hemoglobinopathies including sickle cell
    disease and β-thalassemia [35], malaria [36],
  • spinal cord injury [37], traumatic brain injury [38,39],
  • altitude sickness [40,41], the
    three classic psychiatric diseases, major depression,
    schizophrenia and bipolar disorder [42–45],
  • gastric ulcers [46,47],
    glaucoma [48], age-related macular degeneration [49],
    cataract [50,51],
  • pathophysiological responses to herpes
    activation [52] and
  • benign prostatic hyperplasia [53,54].”
  • Nrf2 was reported to lower skin sensitization produced by sensitizing chemicals [57,58].” — (“skin sensitization..” – this likely refers to chronic itch type of conditions that are exacerbated by chemicals that activate TRP channels, which I discuss in more detail in a series of posts. TRP channels are also a big topic that could use more discussion time: (2, 3, 4, 5,))
  • See page 3, for the quotes and see the citation list of the pdf for the [__] references: (1).

Those are some common and severe conditions – so why aren’t we all aware of Nrf2? I don’t know. Possibly because the suggested treatment by the research discoveries are simple dietary changes which are not high profit margin treatments. However the list of foods that may help happens to overlap with those that I’ve been finding helpful for my own autoimmune and undiagnosed digestive problems. (There is a website with guidance about products that may be falsely claiming to have peer-reviewed studies showing that they are effective as Nrf2 activating compounds 2300 articles are mentioned as having been published on the topic of Nrf2, so I have some reading to catch up on. See: (9).)

So skipping the medical jargon, I’ll share some recipes and menu ideas that incorporate some of these foods and phytonutrients (list from the last post, the phytonutrients were quoted from this pdf: (1)

Specific foods or phytochemicals mentioned to help increase Nrf2 include:

  • sulforaphane from cruciferous vegetables, (such as broccoli and cauliflower);
  • foods high in phenolic antioxidants, (This is a large group including bright yellow and red fruits and vegetables, and deep purple produce. The group includes the subgroup flavonoids which include anthocyanins, flavonols, and it also includes the less familiar subgroup chalcones which are found in the commonly used fruits apples, pears and strawberries. The group also includes aldehydes which are found in vanilla and cinnamon, phenolic acids which include salicyclic acid, and tannins which are found in tea, coffee and wine. Baking cocoa and cherries, beans and whole grains are also mentioned, the summary point would be eat more fruits and vegetables; see: (11))
  • the long-chained omega-3 fats DHA and EPA, (salmon, tuna, sardines, krill oil, ground flax meal, walnuts, hemp seed kernels);
  • carotenoids (especially lycopene), (such as carrots, winter squash, sweet potatoes, cantaloupe, apricots, and lycopene is in tomato, watermelon, pink grapefruit, guava); 
  • sulfur compounds from allum vegetables, (such as onions, garlic, shallots, green onions); 
  • isothiocyanates from the cabbage group and
  • terpenoid-rich foods. (Terpenes are found in real lemon and lime oil, rosemary, oregano, basil and other aromatic green herbs).
  • The Mediterranean and the traditional Okinawan Diets are also mentioned as being Nrf2 promoting diets. See: (wakeup-world.1)

Menu ideas, a start –

  • Add more fruits and vegetables to any meal or snack.
  • Add a dash of real lemon or lime juice to salads or soups. A large spoonful can help aid digestion as we reach middle age. The digestive system tends to produce less natural acidity and it is needed for better absorption of B vitamins. Or sprinkle fresh lemon or lime zest grated from the peel or add a teaspoon of Ground Dried Lemons / Citron Seche Moulu / Limon Seco Molido which may be available at an India foods market. A spoonful of apple cider vinegar or other food grade vinegar could also aid digestion but would not provide the terpenoids found in lemon or lime oil. High quality apple cider vinegar or wine vinegar may contain other beneficial phytonutrients from the phenolic group from the above list as apples and wine are sources of some types.
  • Add a teaspoonful or more or less or any, to taste, of dried green leafy herbs to your salad or soup for aromatic terpenoids and likely phenolic phytonutrients as well; such as Basil, Cilantro, Italian Seasoning, Tarragon, Thyme. Basil and Cilantro are mild and are also used fresh in larger amounts as part of the salad greens. Basil is used fresh or dried in larger amounts in Pesto sauces. Parsley is also used fresh in larger amounts in Tabouli salads.
  • The herb Rosemary is also a good source of terpenoids but is slightly like pine needles and needs to be added to a dish that will be cooked about 20 minutes for better texture. I enjoy Rosemary with beta carotene rich orange flesh Sweet Potatoes which I cook as a skillet scalloped potato. I first saute an Onion sliced in thin rings (allium group) and then add thinly sliced triangles of Sweet Potato so they cook fairly quickly and a teaspoon to a tablespoon of Rosemary. Rosemary is strongly flavored and accidentally spilling too much in the pan can leave the dish inedible, scoop out the excess.
  • Rosemary is a medicinal herb which may help with pain and in traditional folk medicine has been used as a strong tea for pain and inflammation conditions but several cups can have a diuretic effect similar to too much coffee.
  • While discussing hot beverages, Herbal Teas, Green Teas and Black Teas, and Coffee provide phenolic phytonutrients and other antioxidants.
  • Chamomile is a medicinal herb that is frequently used as an Herbal Tea. It has been studied in animal based cell research to increase Nrpf2. (10) The amount used in a cell based study is not something that I could calculate a human recommended serving size for but the traditional medicinal information is available here: (12), caution against its use for asthma, and some seasonal allergy sufferers is mentioned and it is not recommended for use in pregnancy due to a possible risk of miscarriage. Chamomile is a tiny daisy like flower with white petals and a yellow center. The bright yellow center may be a source of phenolic nutrients. (11) Medicinal uses mention digestive and skin complaints, inflammation, relief from muscle contractions, particularly in the intestines, and relief from anxiety. (12)
  • Baking Cocoa is also a source of some phenolic and antioxidant nutrients and can quickly be made into a cup of Hot Cocoa by boiling  a cup of water and adding one or two large spoonfuls of the baking cocoa powder, to taste, along with a spoonful of sweetener. If richness is desired a half teaspoon of Coconut Oil can be stirred in for a hint of creaminess. Less processed/cold pressed Coconut Oil is also a source of phenolic nutrients. (6)
  • Sugar itself can be a source of inflammation so limiting sugar in beverages or other foods is generally a good idea for a health promoting menu plan.
  • Wine can be a source of phenolic nutrients, however it can also be a migraine trigger for some migraine sufferers (like me). Some of the benefits of wine are provided by the free (not-bound-within-a-larger-protein) amino acid content and other free amino acids in wine may be part of the migraine cause. Due to a genetic difference I found a bulk supplier of powdered free amino acids and tried Methionine and Glycine in water. A half teaspoon of each provides a cheerful mood boost without causing excess energy boosting effects – I tried a teaspoon of each initially and it could cause sleeplessness if taken late in the evening and almost too much of a energy boost to the point of increased heart rate. The free amino acids are acidic and cause a puckery tart wine effect. Adding an ounce or two, 2-4 Tablespoons of a 100% purple grape juice or cherry juice or black currant juice could add a hint of sweetness and makes the beverage slightly more juice or wine like. A deficiency of Methionine whether due to a genetic difficulty in metabolism such as I have or due to a dietary lack can increase the body’s need for Nrf2. (7) A deficiency of Nrf2 could negatively effect the body’s supply of the amino acids glycine and serine and it is involved in their biosynthesis pathways. (13) The pathway, called the pentose phosphate pathway, is shown in Figure 2: (14). So speculatively glycine wouldn’t be helping make Nrf2 but if there was a problem with supply of Nrf2 then there might be a shortage of glycine or serine, and they do have biological roles throughout the body.

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.

  1. Martin L Pall, Nrf2, a master regulator of detoxification and also antioxidant, antiinflammatory and other cytoprotective mechanisms, is raised by health
    promoting factors., Stephen Levine, Acta Physiologica Sinica, February 25, 2015, 67(1): 1–18  http://www.actaps.com.cn/qikan/manage/wenzhang/2015-1-01.pdf (1)  // quoted in: Joseph Mercola, The Harmful Effects of Electromagnetic Fields Explained, wakeup-world.com, Dec. 22, 2017, https://wakeup-world.com/2017/12/22/the-harmful-effects-of-electromagnetic-fields-explained/ (1)
  2. https://effectiveselfcare.info/2017/10/15/g3-5-negative-stress-chemicals-may-cause-symptoms-like-itching-migraines-pain-or-ibs/ (2)
  3. https://effectiveselfcare.info/2017/10/15/antihistamines-may-help-if-genetic-tendency-overproduce-histamine/ (3)
  4. https://effectiveselfcare.info/2017/10/15/g3-6-1-calcium-sparklets-and-oxidative-stress/ (4)
  5. https://effectiveselfcare.info/2017/10/15/trpv-channels-comfort-vanilla-heat-capsaicin/ (5)
  6. Marina AM, Man YB, Nazimah SA, Amin I.,  Antioxidant capacity and phenolic acids of virgin coconut oil. Int J Food Sci Nutr. 2009;60 Suppl 2:114-23. https://www.ncbi.nlm.nih.gov/pubmed/19115123 (6)
  7. Lin AH, Chen HW, Liu CT, Tsai CW, Lii CK., Activation of Nrf2 is required for up-regulation of the π class of glutathione S-transferase in rat primary hepatocytes with L-methionine starvation., J Agric Food Chem. 2012 Jul 4;60(26):6537-45. https://www.ncbi.nlm.nih.gov/pubmed/22676582 (7)
  8. Yu-Kun Jennifer Zhang, Kai Connie Wu, Curtis D. Klaassen, Genetic Activation of Nrf2 Protects against Fasting-Induced Oxidative Stress in Livers of Mice., March 18, 2013http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059122 (8)
  9. Which Nrf2 Products have Peer-Reviewed Studies – Beware of Phony Science, nrf2.comhttp://www.nrf2.com/?page_id=38 (9) Stuff to read later list: */Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity. */Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice. */Effects of a Water-Soluble Curcumin Protein Conjugate vs. Pure Curcumin in a Diabetic Model of Erectile Dysfunction. */Curcumin enhances non-opsonic phagocytosis of Plasmodium falciparum through up-regulation of CD36 surface expression on monocytes/macrophages. */Function and regulation of the Cyp2a5/CYP2A6 genes in response to toxic insults in the liver.– Curcumin is a vitamin/hormone D analog and is an extract of the root vegetable Turmeric which provides the bright yellow color to Indian curry spice mixes. CYP enzymes are actively involved in vitamin/hormone D metabolism.  /Yes, Vitamin D is needed to produce Nrf2: (15)/ */Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation. – so yes, speculatively, a deficiency might increase risk of fatty liver disease. */Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria. */Extremely low-frequency electromagnetic fields activate the antioxidant pathway Nrf2 in a Huntington’s disease-like rat model. */Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. */Chamomile Confers Protection against Hydrogen Peroxide-Induced Toxicity through Activation of Nrf2 -Mediated Defense Response.
  10. Bhaskaran, Natarajan & Shukla, Sanjeev & Gupta, Sanjay. (2012). Abstract 2594: Chamomile (Matricaria chamomilla L.) upregulates heme oxygenase-1 through activation of ERK-Nrf2 signaling: Cytoprotective mechanism against oxidative damage. Cancer Research. 72. 2594-2594. 10.1158/1538-7445.AM2012-2594. https://www.researchgate.net/publication/275442168_Abstract_2594_Chamomile_Matricaria_chamomilla_L_upregulates_heme_oxygenase-1_through_activation_of_ERK-Nrf2_signaling_Cytoprotective_mechanism_against_oxidative_damage (10)
  11. Maria de Lourdes Reis Giada, Chapter 4: Food Phenolic Compounds: Main Classes, Sources and Their Antioxidant Power, Biochemistry, Genetics and Molecular Biology » “Oxidative Stress and Chronic Degenerative Diseases – A Role for Antioxidants”, book edited by José A. Morales-González, ISBN 978-953-51-1123-8, Published: May 22, 2013    https://www.intechopen.com/books/oxidative-stress-and-chronic-degenerative-diseases-a-role-for-antioxidants/food-phenolic-compounds-main-classes-sources-and-their-antioxidant-power (11)
  12. Roman Chamomile, Penn State Hershey Medical Center, http://pennstatehershey.adam.com/content.aspx?productId=107&pid=33&gid=000233 (12)
  13. Gina M. DeNicola, Pei-Hsuan Chen, Edouard Mullarky, Jessica A. Sudderth, Zeping Hu, David Wu, Hao Tang, Yang Xie, John M. Asara, Kenneth E. Huffman, Ignacio I. Wistuba, John D. Minna, Ralph J. DeBerardinis, and Lewis C. Cantley., NRF2 regulates serine biosynthesis in non-small cell lung cancer., Nat Genet. 2015 Dec; 47(12): 1475–1481.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721512/ (13)
  14. Albena T.Dinkova-KostovaAndrey Y.AbramovThe emerging role of Nrf2 in mitochondrial function., Free Radical Biology and Medicine, Vol 88, Part B, Nov 2015, Pages 179-188, Part of special issueNrf2 Regulated Redox Signaling and Metabolism in Physiology and Medicine Edited by 
    G E Mann, H J Forman, M Yamamoto, T Kensler, J D Hayes,

    https://www.sciencedirect.com/science/article/pii/S0891584915002129 (14)

  15. K Nakai, H Fujii, K Kono, S goto, R Kitazawa, S Kitazawa, M Hirata, M Shinohara, M Fukagawa, S Nishi, Vitamin D Activates the Nrf2-Keap1 Antioxidant Pathway and Ameliorates Nephropathy in Diabetic Rats., American Journal of Hypertension, Volume 27, Issue 4, 1 April 2014, Pages 586–595, https://academic.oup.com/ajh/article/27/4/586/2743232 (15)