Nrf2 – Page 6 – TranscendingSquare

February 2, 2018

For those who can’t grow pomegranates, consider sumac instead

Sumac is a shrub like tree or a tree like shrub that is an invasive plant in many areas. Types that have white berry clusters should be avoided as the white berries are poisonous but the types with clusters of red berry like seeds are safe to consume when made into a tea and they may be dried and ground into a spice. Native Americans use them in a lemonade like beverage and they are ground into a spice which is used in many Middle Eastern dishes and as a table condiment to sprinkle on foods to individual taste. The ground Sumac is mixed with salt or available plain in shaker bottles and is mixed with a few other spices in the blend called za’atar (sesame seed, salt, and thyme or hyssop).

Some of the phytonutrient content and medicinal properties of edible sumac are similar to those found in pomegranate and may be associated with the bright red pigmentation. The botanical name for Sumac , ‘Rhus,’ translated as a foreign word means ‘red.’ Some people may be allergic skin reactions from touching the plant in nature (1) and as a more concentrated tea it has diuretic properties, which can have health benefits to help remove toxins if plenty of additional water is also consumed to prevent dehydration. (2)

“Sumac is used medicinally in Arab countries. Studies on sumac extracts to date have indicated that the plant may be a source of bioproducts with the following bioactivities: antifibrogenic, antifungal, anti-inflammatory, antimalarial, antimicrobial, antimutagenic, antioxidant, antithrombin, antitumorigenic, antiviral, cytotoxic, hypoglycaemic and leukopenic (Rayne and Mazza, 2007).” (1)

The lemonade like flavor would be from the terpene limonene and possibly other terpenes found in the plant. Anthocyanins likely give it some of the bright color. It also contains tannins primarily in the form of gallotannins, which are similar to the elligatannins/ellagic acid found in pomegranate, (3), and other aldehydes and beneficial acids that give it tartness including vitamin C – ascorbic acid. (1) Eating a large enough amount on a regular basis may be important for the health benefits from phytonutrients. Research with elligatannins has found them helpful for cancer prevention and somewhat for treatment (4) but a recent study that used a small dose, 900 mg of pomegranate extract per day, found some changes in important genes but not conclusive health benefits. (5) Research on tumor inhibiting properties of sumac found it beneficial during early stages when the tumor is developing rather than as a treatment after it was formed (animal study). (6) Animal based trials in more recent research that found benefits using pomegranate extract used doses that would be equivalent to larger doses, 1 to 10 grams/kilogram body weight per day. The study and amounts used are discussed in this post and the link is in this earlier post. A beneficial substance that we have to make for ourselves, Nrf2 may be involved. Tannins, anthocyanins, and aldehydes were all mentioned as being helpful for helping promote our own body’s ability to produce more Nrf2. The gallic acid (related chemically to the gallotannins, the mango fruit is also a source (8)) is mentioned to help induce apoptosis in cancer cells (cell death) in an article discussing the role of oxidative stress in cancer treatment. (7)

“Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a polyhydroxy phenolic compound, is abundant in natural plants such as gallnut, grapes, sumac, oak bark, green tea apple peels, grapes, strawberries, pineapples, bananas, lemons, and in red and white wine. Its antioxidative DNA-damage action has been well documented [122]. However, gallic acid induces apoptosis in several cancer cell lines by increasing ROS level and GSH depletion [123].” (7)

That excerpt is from a section titled: 5.1. Anticancer ROS-Generating Compounds from Natural Origin, (7), which also contains information on other phytonutrients and foods that contain them that have been found beneficial for preventing or treating cancer or reducing oxidative stress.

I bought some dried sumac prepared for table use but chose a brand without salt added to it so I could use as much as I want without having to be concerned about adding too much salt. The aroma and flavor are good and the color is very pretty, slightly more purplish than paprika but similar in the bright addition it makes when sprinkled on the surface of a food. It was $3.99 for a 9.33 ounce bottle at a Middle Eastern foods grocery store.

Phytonutrients with bright colors often seem to be associated with health benefits but that doesn’t mean all wild berries or plants are edible. Read guides and know what you’re harvesting before eating it – and avoid private property and nature preserves where it might be illegal to pick anything.

They are so common in some areas that I happen to have picture taken on a recent walk. A discussion with more detail and a close up image taken during late summer is available here: The ‘Lemonade Tree’: It’s Time to Harvest Sumac, EdibleEastEnd.com. (2)

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.

Sumac – an overview, ScienceDirect Topics, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/sumac
Ronald Halweil, The ‘Lemonade Tree’: It’s Time to Harvest Sumac, Edible East End, August 9, 2012, EdibleEastEnd.com, https://www.edibleeastend.com/2012/08/09/harvest-sumac/
J. P. Perchellet, H. U. Gali, E. M. Perchellet, P. E. Laks, V. Bottari, R. W. Hemingway, and A. Scalbert, Antitumor-Promoting Effects of Gallotannins, Ellagitannins, and Flavonoids in Mouse Skin In Vivo,
Food Phytochemicals for Cancer Prevention, Chapter 25, pp 303–327

Chapter DOI: 10.1021/bk-1994-0546.ch025, ACS Symposium Series, Vol. 546, http://pubs.acs.org/doi/abs/10.1021/bk-1994-0546.ch025
Tariq Ismail, Cinzia Calcabrini, Anna Rita Diaz, Carmela Fimognari, Eleonora Turrini, Elena Catanzaro, Saeed Akhtar, and Piero Sestili,
Ellagitannins in Cancer Chemoprevention and Therapy. Toxins (Basel). 2016 May; 8(5): 151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885066/
Nuñez-Sánchez MA, González-Sarrías A, García-Villalba R,et al, Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem. 2017 Apr;42:126-133. doi: 10.1016/j.jnutbio.2017.01.014. Epub 2017 Jan 27. https://www.ncbi.nlm.nih.gov/pubmed/28183047
Perchellet, J.P., Gali, H.U.Perchellet, E.M.Laks, P.E.et al., Antitumor-promoting effects of gallotannins, ellagitannins, and flavonoids in mouse skin in vivo [1994], ACS symposium series, ISSN : 0097-6156, Source: Information Systems Division, National Agricultural Library, http://agris.fao.org/agris-search/search.do?recordID=US9602151
Giuseppina Barrera, Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy., ISRN Oncol. 2012; 2012: 137289.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483701/
Gallotannins, Science Direct, ScienceDirect.com, https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/gallotannins

January 4, 2018January 14, 2018

Why care about health? It’s about statistics.

The rate of cancer incidence has increased greatly in many countries and is expected to continue to increase, particularly in association with the aging of the population. Cancer is more often a diagnosis after age 65. The rate of thyroid cancer in particular has increased greatly in women. The rate of developing some type of cancer during one’s lifetime is expected to reach 1 in 2 men and 1 in 3 women by the yea 2050, (MedScape) – or a more general 1 in 2 people, (medicalnewstoday) – those are not good odds.

It is common during youth to feel secure about health but our bodies tend to run out of stored nutrients as we age and metabolic pathways that we depend on to rebuild muscle and remove toxins or defective cells can become less effective. A healthy immune system also protects us from our own body’s normal rebuilding/regrowth of new cells. Defective ones are typically removed from growth areas in bone marrow before they enter circulation. Cancer cells are also removed on a regular basis when our immune systems are healthy.

Magnesium deficiency is a topic I keep stressing because the immune cells require magnesium in order to perform the apoptosis, killing, of defective or precancerous cells. The body’s defense systems are well developed but need fuel on a daily basis in order to be able to function as nature designed. While immune cells need magnesium in order to purposefully kill defective cells by apoptosis ( an enzyme is inserted into the cell which causes it to die and then the immune cell engulfs the debris and removes it for detoxification and excretion from the body), a cell that is deficient in magnesium or calcium may also undergo apoptosis due to the deficiency. (magnesium and apoptosis)

Too little Nrf2 may reduce immune system and antioxidant health but too much can be a problem in cancer cells that grow too rapidly. (Nrf2 overproduction and cancer)

Another person writing about the recent research in the area of Nrf2 shares more information about foods that help promote Nrf2 and how nature may have built in a mechanism within some foods that help prevent an over production of the important protein (Nrf2). See: “Activate Nrf2, then optimize: Brussel Sprouts.” – Bill Lagokos (patreon) /Spoiler, if not a fan of Brussel Sprouts the healthy phytonutrient that is discussed is also found in cruciferous vegetables including cabbage, cauliflower, broccoli, kohlrabi, and kale.

I personally am more sensitive to the group, especially if served raw or in larger quantities, but find steamed kale everyday tolerable to my digestive system. The bloating effect may be due to our good guy bacteria enjoying the fiber rich vegetables so much they produce the excess gas – but it can be a sign of healthy bacteria in our digestive tract. Irritable Bowel Syndrome can be affected by any food that causes bloating effects possibly due to TRP channel’s being activated by increased pressure. People with a history of IBS and other chronic pain syndromes may be suffereing from an underlying issue with overactive TRP ion channels. IBS and TRP channels are discussed on this site in a previous post. TRP channels are discussed in more detail with links on another website: Chronic Itch, migraines, IBS and stress; – that is one part frm a longer series: Relaxation and Stress, which is continued in: Preeclampsia & TRP Channels.

December 28, 2017December 28, 2017

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.^63″(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.

DaigoSumi, AikoManji, YasuhiroShinkai, TakashiToyama, YoshitoKumagai., 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. 223, Issue 3, 15 September 2007, Pages 218-224. http://www.sciencedirect.com/science/article/pii/S0041008X07002633 (1)
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)
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)

December 24, 2017February 1, 2018

It is not a coincidence that my phospholipid rich diet overlaps with Nrf2 promoting foods

The punchline – phospholipids are the building block of cannabinoids which are also a phytonutrient that causes an increase in production of Nrf2. (1, 3) The most concentrated source of cannabinoids or phospholipids is found in medical marijuana or the non-euphoric CBD oil which is more likely to be available legally. However there are other legal sources of phospholipids and cannabinoids. The phytonutrients are also found in cocoa beans/baking cocoa/dark chocolate (processing reduces the concentration and availability of the ‘bitter’ tasting nutrients in more processed milk chocolate and chocolate syrup.) Phospholipids add a slight bitter taste to foods which I’ve always been able to taste and tend to prefer. A genetic screening did find that I have a double/ both sets of genes/ difference in my ability to make any chemical with phosphorus – the phospho- part of phospholipids which are important in many chemicals in the body not just cannabinoids. (4 – an open access textbook on phosphorylation)

For example the original Lemonhead TM candies have more flavor to me than the more recent version of lemon flavored Chewy Lemonhead, (lemonhead.com). Bitterness is something we have a specialized set of tastebuds to detect. Our tastebuds have a few specific types and there are some that detect sweet, salty, sour, bitter, and some for Umami (fermented protein/free amino acid/a hint of soy sauce like flavor). Recently reseachers have suggested a set detect starch but sweet is also a starch so it might be similar to the sweet detecting tastebuds. The article explains that the difference between simple sugars and complex, longer chain carbohydrates called polysaccharides, can be detected suggesting there are two types of carbohydrate sensing tastebuds. (2)

Our sense of smell adds a lot more differences to our enjoyment of foods and beverages. Terpenes are particularly good smelling and other phenolic compounds also add aroma. Cinnamon and vanilla, basil, oregano and lemon are all sources of phenolic compounds or terpenes. These were discussed in more detail in the recent post on Nrf2 and diet tips for promoting Nrf2. It is a protein that causes genes that make important antioxidants to become active so it helps protect us against damage from oxidative stress which can be caused by health factors or by real world worries whether an upsetting conversation or bad traffic.

Pomegranate seeds (not the juice) and pumpkin seed kernels are also good sources of phospholipids. The spice cardamom powder is also a good source. See the section The DASH Diet and Pumpkin Seeds on the home page of my other website: effectivecare.info. A salad recipe and more information about genetics and cannabinoids are also available on that site or in the post Is it Starvation or Addiction?

Pomegranate extract has been studied in animal based research to examine in more detail how it helps hypertensive blood pressure problems and reduce oxidative stress. The mechanism was found to involve increasing Nrf2. The formation of mitochondria increased, and their function improved. Before treatment the hypertensive animals had fewer of the specialized proteins that are involved in production of mitochondria. Mitochondria are the cellular organelles primarily responsible for turning blood sugar/glucose into usable energy. (5)

This study uses a pomegranate extract that incorporates the peel, seeds and juice as all contain the bioactive phytonutrient, punicalagin, thought to be most helpful for anti-inflammatory, anti-tumor and anti-diabetic effects. The animals who received the extract were found to have better blood pressure, reduced heart hypertrophy ( a sign of worse heart health) and a lower heart rate. Neuronal/nerve cell activity and oxidative stress markers were decreased in the experimental treatment group compared to the control group which received a saline solution and no pomegranate extract. Angiotensin converting enzyme which is involved in blood pressure control was lower in the experimental group that received pomegranate extract and may be the mechanism for the lower blood pressure. Pro-inflammatory cytokines were reduced in the experimental group after treatment, an indication that hypertensive inflammation was reduced. The pomegranate extract treatment led to increased levels of phosphorylated AMPK which then leads to an increase in Nrf2 and its resulting increases in antioxidant proteins which protect against injury and inflammation from oxidative stress chemicals. (5)

Pomegranate is referred to as an ancient fruit in a research study on its benefits against hepatocellular carcinoma. Spoiler alert – it was found beneficial. (6)

“PE (Pomegranate Extract) treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC (Hepatocellular Carcinoma).” (6)

One to ten grams per kilogram (1 to 10 g/kg) (6) gives us a quantity but that is of the extract which is made with the juice, seeds and peel. The inner peel is whitish in color while the outer peel is vibrantly colored similarly to the juice. An average adult weighs somewhere around 70 kg (68 kg ~ 150 pounds) so the animal study used an equivalent of 70 to 700 grams of pomegranate extract. Five grams is about a teaspoon so 70 grams would be slightly less than 5 Tablespoons or about 1/4-1/3 cup which is roughly a half a pomegranate worth of seeds with the juice and would be a reasonable serving size. Ten times that would be more than a typical serving at approximately two and a half to three and a third cups of pomegranate extract per day, for 22 weeks (6) – but if you have Hepatocellular Carcinoma that might sound good compared to other chemotherapy treatments.

My health and anxiety seems to be improved with a half a pomegranate worth of the seeds per day, or half in the morning and half in the evening when anxiety is worse. I have not tried using any part of the peel or interior whitish colored membranes so I don’t know what how edible they would taste. Pumpkin seed kernels are a higher fat food and the serving size is about 2 to 4 tablespoons, 1/8 to 1/4 cup as a snack my themselves or sprinkled on a salad. I prefer to have some of both foods every day. As well as other dark green leafy vegetables and herbs, beans, rice, nuts and other seeds, and ground lemon powder and/or lime or lemon juice. One healthy food alone isn’t enough to improve my health and mood on it’s own however the half a pomegranate can improve my mood when I’m having a worse anxiety moment. Pumpkin seed kernels are a higher fat and protein substance and don’t seem to have the quick acting mood lifting effect but I notice when I run out of them and don’t have any for a few days.

Regarding the “ancient fruit” reference in (6), yes pomegranate is mentioned in the Bible, Old Testament; 1 Samuel 14.2, “Saul was staying in the outskirts of Gibeah under the pomegranate tree…” and Old Testament; Haggai 2.19: “Is the seed yet in the barn? Do the vine, the fig tree, the pomegranate, and the olive tree still yield nothing? From this day on I will bless you.” Also pomegranates are mentioned as a decorative feature in a church: “House of the Lord” Jeremiah 52.17, 52.20-23 “As for the two pillars, the one sea, the twelve bronze bulls which were under the sea, and the stands, which Solomon the king had made for the House of the Lord, the bronze of all these things wre beyond weight. 21 As for the pillars, the height of the one pillar was eighteen cubits, its circumference was twelve cubits, and its thickness was four fingers and it was hollow. 22 Upon it was a capital of bronze; the height of the one capital was five cubits; a network and pomegranates, all of bronze, were upon the capital round about. And the second pillar had the like, with pomegranates. 23 There were ninety-six pomegranates on the sides; all the pomegranates were a hundred upon the network round about.” (7) So it seems pomegranates were thought quite valuable during Biblical times.

Menu tips to be continued later, Happy holidays!

Li X., Han D., Tian Z., Gao B., Fan M., Li C., Li X., Wang Y., Ma S., Cao F.,
Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice., Cell Physiol Biochem 2016;39:1521-1536, https://www.karger.com/Article/FullText/447855 (1)
Chase Purdy, The human tongue has a sixth sense and its a taste bud that loves carbs. Quartz, qz.com, Sept. 8, 2016, https://qz.com/776857/the-human-tongue-has-a-sixth-sense-and-its-a-taste-bud-that-loves-carbs/ (2)
Wang Y, Ma S, Wang Q, Hu W, Wang D, Li X, Su T, Qin X, Zhang X, Ma K, Chen J, Xiong L, Cao F: Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci China Life sci 2014;57:201-208. https://www.ncbi.nlm.nih.gov/pubmed/24430557 (3)
Claude Prigent, Editor, Protein Phosphorylation, Publisher: InTech, Chapters published November 29, 2017 under CC BY 3.0 license InTechOpen.com, https://www.intechopen.com/books/protein-phosphorylation (4)
Wenyan Sun, Chunhong Yan, Bess Frost, Xin Wang, Chen Hou, Mengqi Zeng, Hongli Gao, Yuming Kang,and Jiankang Liu,
Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats., Sci Rep. 2016; 6: 34246. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054377/ (5)
Anupam Bishayee, Deepak Bhatia, Roslin J. Thoppil, Altaf S. Darvesh, Eviatar Nevo, and Ephraim P. Lansky., Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms., Carcinogenesis. 2011 Jun; 32(6): 888–896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314278/ (6)
Holy Bible, Revised Standard Version, Containing the Ole and New Testaments, Thomas Nelson & Sons, New York, 1952, 1 Samuel 14.2, page 297, Haggai 2.19, page 984 https://www.amazon.com/1952-Revised-Standard-Version-Bible/dp/B000U2L3E0 (7)