G10: Nrf2 promoting Foods

Nrf2 is the easy way to say the long chemical name of a protein that promotes an increase in gene activity of a gene with a similar long name - Nrf2 stands for the nuclear factor E2-related factor 2  - a name so long it has its own abreviation - E2 stands for erythroid-2 or erythroid-derived 2. It is important enough for health however that it is worth trying to remember the short or long name because it helps protect our body from our own oxidative stress or external causes of oxidative stress. Reducing oxidation helps protect against cancer and other inflammatory conditions. 

     Every cell of our body has to produce energy every day, all day, and during that production waste products are made that have to be detoxified and excreted or recycled for additional use. When nutrients or water or organ health are insufficient for the daily detoxification process then the waste products can collect and lead to damage in the cells. Over time the damage can lead to different types of scarring and result in long term damage that can not be repaired by the body as easily as simply clearing out waste products through our excretion systems.

     The science is complicated but the solution for helping the body produce more Nrf2 is delicious - colorful fruits and vegetables, flavorful herbs and spices, and wholesome grains, beans, nuts and seeds.

     This section is going to discuss the foods that may help promote Nrf2 and leave the complicated science for the scientists, but first, a list is included of the health conditions that Nrf2 may have a role in preventing or treating. People with these conditions may find relief by eating more of the foods that are discussed later. This is a new area of research and finding individual health care providers who are familiar with the area of study may be difficult however many are familiar with strategies to increase the use of fresh produce and whole grains and beans. Cookbooks and cooking classes can also be helpful and fun. 

The role of Nrf2 “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  (G10.25), including Alzheimer’s, (G10.24), 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 (G10.1) – 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 (G10.8))
• 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: (G10.1). 

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: (G10.2, G10.3, G10.4, G10.5,))

See page 3, for the quotes and see the citation list of the pdf for the bracketed [__] references: (G10.1). 

     To summarize in simpler terms - reducing oxidative stress by promoting Nrf2 protein and increased gene activity might be helpful to protect against hemoglobin conditions such as sickle cell anemia, malaria and beta-thalassemia; traumatic brain or spinal cord injury; sickness symptoms associated with being at high altitudes - in the mountains or on an airplane possibly; mental health conditions of depression, schizophrenia and bipolar disorder; stomach ulcers; eye diseases associated with aging such as glaucoma, macular degeneration and cataract; symptoms associated with herpes lesions; prostate gland enlargement; sensitive skin reactions which may suggest chronic itch type conditions. 

So skipping over the medical jargon and moving onto the chemical jargon, a list is available of phytochemicals/nutrients found in plants that have been found to help promote Nrf2 production. I’ve added some specific food examples with the list of chemical groups. Each type of phytonutrient may have several or many individual examples that differ slightly between plants but chemically act similarly to each other. Later I will share some recipes and menu ideas that incorporate some of these foods and phytonutrients. (The list of phytonutrients were quoted from this pdf: (G10.1)

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: (G10.11))
• the long-chained omega-3 fats DHA and EPA, (salmon, tuna, sardines, krill oil, ground flax meal, walnuts, hemp seed kernels);
• carotenoids (especially lycopene), (beta-carotene is found in carrots, winter squash, sweet potatoes, cantaloupe, apricots; and lycopene is in tomato, watermelon, pink grapefruit, guava; to name a few sources); 
• sulfur compounds from allum vegetables, (such as onions, garlic, shallots, green onions); 
• isothiocyanates from the cabbage group (such as Brussel sprouts, cabbage, kale)
• and terpenoid-rich foods. (Terpenes are found in real lemon and lime oil, sumac,  rosemary, oregano, basil and other aromatic green herbs).

The Mediterranean and the traditional Okinawan Diets are also mentioned as being Nrf2 promoting diets. See: (G10.1.1) 

• 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.
• Add a couple tablespoons of sesame seeds or pumpkin seeds to a salad or on other foods where a little crunch might be enjoyable. 
•  Sesame seeds, or tahini, sesame paste, has been shown in sports research to help reduce oxidative stress. The trial subjects ate 2 tablespoons per day of the seeds. Tahini paste is thinner than peanut butter but can be used on bread or a rice cake in a similar way. The flavor is strong however and does not pair as well with sweet jams or jellies but I enjoy it with ginger powder or a drizzle of blackstrap molasses. Effects of Sesame (Sesamum indicum L.) Supplementation on Creatine Kinase, Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi-Professional Soccer Players. 

• 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.

• The herb Rosemary, mentioned in the last menu idea, 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 Nrf2. (G10.10) 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: (G10.12), 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 phenolicnutrients. (G10.11) Medicinal uses mention digestive and skin complaints, inflammation, relief from muscle contractions, particularly in the intestines, and relief from anxiety. (G10.12)
• 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. (G10.6)
• 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 and beer can provide some phenolic nutrients, however they can also be a migraine trigger for some migraine sufferers (like me). Some of the mood lifting benefits of wine are provided by the free (not-bound-within-a-larger-protein) amino acid content found in wine while other free amino acids in wine may be part of the migraine cause.  

     Due to a genetic difference I discovered that I have, 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 having an increased heart rate. Several free amino acids act within the brain to activate or inhibit neurons/brain cells.

     The free amino acids are acidic and cause a puckery tart wine or lemonade effect when added to water. Adding an ounce or two of juice, 2-4 Tablespoons of a 100% Purple Grape Juice or Cherry Juice or Black Currant Juice, can add a hint of sweetness and anthocyanins and makes the resulting 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. (G10.7) A deficiency of Nrf2 could negatively affect the body’s supply of the amino acids Glycine and Serine as it is involved in their biosynthesis pathways. (G10.13) The pathway, called the pentose phosphate pathway, is shown in Figure 2: (G10.14). 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. Glycine also has roles in the brain to inhibit overactivation and therefore may help if anxiety or other mental illness symptoms are present.

Yes, but what about the Wine and Beer? - Two servings of alcoholic beverages for a man or one for a smaller woman or man has been found to provide some cardiovascular health benefits - enjoy responsibly and designate a driver if time isn’t available to detoxify the alcohol, approximately one hour per serving is needed to recover from the physical effects of alcohol on thinking and reaction time. Whiskey and other liquors may also contain some beneficial nutrients depending on the ingredients and processing and age of the liquor.  (G10.26) The serving size of alcoholic beverages varies based on the concentration of alcohol.  Serving sizes and more information about the medical research regarding alcohol is available on the Harvard T. H. Chan School of Public Health website: Alcohol: Balancing Risks and Benefits. (P.alcohol) 

     Fermenting fruit and other starchy plants or grains was a way to preserve the nutrients when there was no freezer or refrigerator. Jagermeister is a flavorful alcoholic beverage that was sold as a cough medicine and digestive aid. It may have health benefits because of the many nutritious seasonings used in the recipe  (G10.27)  but moderation is still important with alcoholic beverages. Some people have trouble stopping once they start drinking and none might be the best serving size for them.  

See the section I: Addiction or Starvation? For more information about a possible genetic difference that may be involved in addictive alcohol or other substance use.

When more liquid from juice or pomegranate extract is used in place of part of the coconut oil/butter ingredient, the cookie recipes included in G8: Cookies & Bean Soup can be modified into a slightly lower sugar and lower fat version that bakes up as moist Brownie or Fudge like cookies. The emulsifying power of eggs can be made with Golden Flax Meal as was described in G8: Cookies & Bean Soup or the powdered spice called Gumbo File also can be used in place of eggs when prepared similarly to the Golden Flax Meal technique. Both Gumbo File powder and Golden Flax Meal are Nrf2 promoting ingredients and might help protect against cancer and other inflammatory conditions.

Cheerful Chocolate Cookies - I called them Cheerful because the Pomegranate Extract ingredient gives me a very cheerful mood - even more cheerful than just having chocolate cookies would provide. The image shows the unbaked cookies and a tray of baked cookies. The chocolate is very dark rather than burnt. Check for doneness by the crispness of the crust rather than watching for much change in the color. This recipe is a double batch compared to the G8: Cookies & Bean Soup recipes. It will make four pans of 24 cookies approximately instead of two pans of 24.

Dry ingredients - measure and mix in a large bowl: 

• 1 1/4 cup Brown Rice Flour
• 3/4 cup Cocoa Powder (Regular or “Dutched” would work similarly)
• 2 cups Coconut Flour
• 1 cup Almond Meal
• 1/2 cup Tapioca Flour/Starch
• 1 teaspoon Salt
• 1 teaspoon Cardamom Powder
• 1 1/4 teaspoon Baking Soda

Emulsifier step- gently heat Pomegranate Extract or Juice to a simmer in a saucepan then remove from heat and stir in the Gumbo File Powder until the mixture is thickened.

• 1 1/2 cups Pomegranate Extract
• 6 Tablespoons Gumbo File Powder

Wet ingredients – in a another large bowl combine the thickened warm emulsifier liquid with the Brown Sugar and then stir in half of the remaining juice. Reserve part of the juice to add to the dry ingredients after first mixing in the emulsifier/sugar mixture. (This method is more like making a cake than a cookie, you combine small amounts of the liquid at a time for a smooth cake batter that is not over-stirred.)

• 2 cups Brown Sugar
• 2 teaspoons Vanilla
• 2 1/2 cups Pomegranate Juice, (100 percent, unsweetened organic is what I used – with the goal of a functional/healing food in mind)

The dough should be moist and able to be rolled or spooned into a sticky round shape that doesn’t crumble – a soft playdough-like consistency.

     The Baking time is longer than for a cookie dough made with butter or coconut oil – 20-25 minutes for those became 30-35 minutes for these Brownie or Fudge like Energy Bites. I bake two pans of 24 cookies at a time and rotate the pans from top shelf to bottom shelf and turned around front to back at 20 minutes to get a more even baking. These low fat juice containing cookies then take an additional 10-15 minutes. My typical coconut oil/ butter cookies are rotated at 15 minutes and then left for another 10-15 minutes. If baking only one tray use the top shelf and rotating the pan is less important as the oven heat is directed at the top and bottom of the pan more evenly.

     Most of the ingredients in this recipe may be providing beneficial phytonutrients that might help promote our own production of NRF2 which then helps promote our own anti-inflammatory and anti-cancer abilities. Health may never have tasted so good – enjoy!

Spicy Molasses Cookie Variation:Dry ingredients - measure and mix in a large bowl: 

• 2 cups Brown Rice Flour
• 2 cups Coconut Flour
• 2 cups Almond Meal
• 1 teaspoon Salt
• 1 teaspoon Cardamom Powder
• 2 1/2 teaspoons Baking Soda

Emulsifier step- gently heat Pomegranate Extract or Juice to a simmer in a saucepan then remove from heat and stir in the Gumbo File Powder until the mixture is thickened.

• 1 1/2 cups Pomegranate Extract
• 6 Tablespoons Gumbo File Powder

Wet ingredients – in a another large bowl combine the thickened warm emulsifier liquid with the Brown Sugar and then stir in half of the remaining juice. Reserve part of the juice to add to the dry ingredients after first mixing in the emulsifier/sugar mixture. 

• 1 cup Brown Sugar
• 1 cup Blackstrap Molasses
• 4 rounded tablespoons minced Candied Ginger
• 2 1/2 cups Pomegranate Juice, (100 percent, unsweetened organic is what I used – with the goal of a functional/healing food in mind)

Cracker or Pancake Variation:

Dry ingredients - measure and mix in a large bowl: 

• 1 1/2 cups Brown Rice Flour
• 1 1/2 cups Coconut Flour
• 1 1/2 cups Almond Meal
• 1 cup Tapioca Starch/Flour
• 1 teaspoon Salt
• 1 teaspoon Cardamom Powder
• 2 1/2 teaspoons Baking Soda

Emulsifier step- gently heat Pomegranate Extract or Juice to a simmer in a saucepan then remove from heat and stir in the Gumbo File Powder until the mixture is thickened.

• 1 1/2 cups Pomegranate Extract
• 6 Tablespoons Gumbo File Powder

Wet ingredients – in a another large bowl combine the thickened warm emulsifier liquid with the Brown Sugar and then stir in half of the remaining juice. Reserve part of the liquid to add to the dry ingredients after first mixing in the emulsifier/sugar mixture. 

• ¼ to 1 cup Coconut Oil, melted amount varied depending on desired richness of pancake or cracker dough
• 2 1/2 cups Water or Pomegranate Juice or Vegetarian Soup Stock for a savory flavor for crackers, for Pancake Batter about double the liquid would be needed for this amount of dry ingredients. Making a half batch might be a better idea.

To form the cracker dough, sprinkle a dry surface with additional almond meal and roll the dough into a ¼ inch thick sheet. The dough may be easier to work with if chilled overnight. Cut into squares or rounds and place on a greased baking sheet. Bake at 350-400’F for 20-30 minutes or until crisp. Let cool and store in an airtight container.

Pictures of the mixing process for making cookies with an emulsifier other than eggs can be seen in G8: Cookies & Bean Soup. An emulsifier is a type of chemical that can mix with water and with oil so it helps to form a baked good that will be stable and instead of crumbly. Before baking it helps the dough or batter mix together more easily when combining oil or melted butter and other liquid ingredients. The Gumbo File powder used in the Cheerful Chocolate Cookies on this page and the Golden Flaxmeal Powder used in the recipes on G8: Cookies & Bean Soup are both vegetarian sources of an emulsifier. 

     It is not uncommon in the plant world for seeds to have some emulsifying ability as phospholipids are a chemical found in membranes that can mix with water and with oil. Phospholipids are found throughout cell membranes and the group of chemicals add flexibility to the membrane when the plant or human cells are alive. Flax Seeds are a good source of essential omega 3 oil and other beneficial oils in addition to being a source of phospholipids and other emulsifying phytonutrients. 

     Mustard seed powder from which we make the yellow table condiment known as mustard also has emulsifying power and it can help the oil and vinegar of a salad dressing to stay mixed together even when egg yolk isn't used. Egg yolk adds the emulsifying power that can make mayonnaise out of oil and vinegar. When allergies are a problem and egg can't be used there are many common foods and recipes that need to be modified or given up by the person with the allergy because egg is used in mayonnaise and other foods as an emulsifier. Wild mustard blooms in spring to early summer and turns to seed by late summer. The pollen may cause seasonal allergy symptoms in sensitive individuals. (G10.30.Wild Mustard) Eating more Nrf2 promoting foods and ingredients such as mustard may help the body to be less sensitive to allergens. Nature has many beneficial plants that human ingenuity has developed into edible and delicious foods.

     The Gumbo File Powder used in the Cheerful Chocolate Cookies earlier on this page is a more unusual source for a baked good but it traditionally has been used to thicken liquids by Native Americans and was originally known as Choctaw Spice and more recently is used in Creole style cooking of Gumbo soups and stews where it became better known as Gumbo File. It is a powder of dried Sassafras Leaves and as Choctaw Spice it was a major export crop during the 1700s from the American colonies, second only to tobacco. (G10.28)

     Sassafras Leaves and Sassafras Root have medicinal value and the root is the original flavoring agent that gives the carbonated beverage Root Beer its name. Sassafras Root was found to have an active ingredient that may promote cancer and the seasonings lost  some of the early popularity. The chemical can be removed from the root and traditionally flavored Root Beer is still available as a specialty item. The chemical is not abundant in the Sassafras Leaves, (G10.28) , so there is no need to avoid using the Gumbo File ins soups and stews - and with the Cheerful Chocolate Cookie recipe I found that it works in baked goods too. The replacement of oil with liquid makes that recipe moister than typical cookies so I wanted to try a more typical style cookie and I've wanted to try Fennel Powder in a baked good - and the result is delicious.

     Fennel Seeds are very nutritious and help with digestion but they are very crunchy and some people with health issues also have pain with chewing. Inflammatory conditions may increase inflammation of the gums. Fennel Powder can be found at specialty spice shops or sometimes at Indian grocery markets. The whole Fennel Seeds are typically available in bulk amounts at Indian grocery markets as they are served whole as an appetizer or left in a dish at the end of a meal somewhat like an after dinner mint. The seeds have a mildly minty flavor mixed with licorice flavor. 

Fennel Cookies:

Wet ingredients:

• 3 Tablespoons Golden Flaxmeal or Gumbo File Powder
• 10 Tablespoons boiling Water
• Stir the Flaxmeal  or Gumbo File Powder into the boiling water in a small bowl for a couple minutes until it thickens and turns opaque slightly. Then add the melted Coconut Oil and stir until it turns creamy white and opaque. Then add the Brown Sugar, Vanilla, and Apple Cider Vinegar.
• 3/4 cup Coconut Oil, melted
• 1 cup Brown Sugar
• 1/2 teaspoon Vanilla
• 2 1/2 teaspoons Apple Cider Vinegar

Dry ingredients, mix together in a large bowl:

• 1 cup Brown Rice Flour
• 3/4 cup Coconut Flour
• 1/2 cup Tapioca Flour/Starch
• 1/2 cup ground Fennel Seed Powder
• 1/2 teaspoon Salt
• 3/4 teaspoon Baking Soda

Add the wet ingredients from the small bowl to the dry ingredients and stir gently until well mixed. The dough will be soft and sticky, moist enough to easily roll or spoon into small rounds. The batch makes two trays of 24 cookies about one inch around.

Coat the pans with a small amount of coconut oil or pan spray to prevent sticking. Bake at 350’F for 25-30 minutes. Rotate the pans from the top and bottom racks at 15 minutes. Let cool on a wire rack and then store in an airtight container in the refrigerator, freezer or at room temperature. Chilling in the refrigerator or freezer will convert the Tapioca starch into a form that can become a healthier form in the digestive system (called resistant starch, (G10.29)).

Lime or Lemon Peel Cookies

Dried lime powder or dried lemon powder are available in Middle Eastern grocery stores. I used two tablespoons of dried lime powder instead of the half teaspoon of vanilla. The flavor blended into the cookie better after a couple days so it might work better if it were added to the melted coconut oil in advance of mixing the cookie dough – melt the oil, mix in the dried lime powder, stir and let it sit for ten or twenty minutes while measuring the other ingredients and then add it to the emulsified Flaxmeal or Gumbo File Powder.

The fennel powder could be replaced with more of one of the other flours or the flavor blended well after couple days and both the lime and fennel have anti-inflammatory phytonutrients content – so give it a try either way and maybe both would be enjoyable.

• 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.
• The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you, at the website eatright.org: (eatright.org/find-an-expert)