Colitis...and Retinoic acid.
This post continues the Retinoic acid theme with a focus on colitis, and IBS or inflammatory bowel selfcare tips and foods.
Retinoic acid induced 16 has a protective role against colitis and cancer associated with inflammatory bowel conditions. (1) It also may have a role in prostate cancer risk as the activity of the Androgen Receptor affects the RAI16 gene. (2)
Often too little of something is a risk and too much is a risk, in health and in life. Deficiency of RAI16 increased the risk of fatty liver developing when eating a high fat diet (animal study). (3) We need RAI16 to help us cope with the oxidative stress effects that Heat Shock Protein 70 helps direct, so that more cells are saved rather than killed by apoptosis. On the other hand, too much of it may be protective for cancer cells to continue multiplying.
In the animal colitis model study, genetically deficient mice without the RAI16 gene were created with CRISPR gene editing techniques. It was found that the loss made the animals more susceptible to a toxin induced colitis, but the animals did not develop colitis spontaneously significantly more than the control group did. But the damage induced by the toxin was much worse and weight loss and tissue changes were seen in the colons of the RAI16 -/- knockout mice. (1)
Retinoid acid induced 16 (RAI16)
RAI16 may be protective in colitis/inflammatory bowel conditions by regulating Heat Shock Protein 70 (HSP70) effects on apoptosis of cells.
“Furthermore, we identified RAI16 as a novel A-kinase anchoring protein (AKAP), which regulated [Heat Shock Protein 70] HSP70 associated anti-apoptosis signaling 13. Homology analysis revealed that RAI16 is highly conserved in multispecies (human, mouse, rat, rabbit or zebrafish, et al.), suggesting that RAI16 might play important roles in cells.” (1)
In hepatocellular carcinoma (HCC) and prostate cancer, the RAI16 gene or protein may be increasing risk of cancer possibly by interaction with the Androgen Receptor.
“Retinoid acid induced 16 (RAI16) was reported to enhance tumorigenesis in hepatocellular carcinoma (HCC). The androgen receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in several cancer progressions. However, whether RAI16 is a candidate AR target gene that may involve in prostate cancer progression was unclear.” (2)
We demonstrate for the first time that RAI16 is a direct target gene of [Androgen Receptor] AR. RAI16 may be involved in cell growth of prostate cancer cells in response to AR signaling.” (2)
So we need some RAI16 activity but not too much. Symptoms of Retinoid Toxicity may include nausea and vomiting but inflammatory bowel trouble is not mentioned as typical, possibly a severe symptom though. (4) Skin rashes on our outer surface indicate there is likely also membrane disrepair internally.
Possible symptoms from a retinoid medication are listed, diarrhea can be a more severe side effect of excess:
“Typical retinoid toxicity include symptoms that are similar to those found in patients taking high doses of vitamin A: Headache, fever, dry skin, dry mucous membranes (mouth and nose), bone pain, nausea and vomiting, rash, mouth sores, itching, sweating, eyesight changes. Plus: Flu-like symptoms, bleeding problems, infections, swelling of feet or ankles, pain (bone and joint pain, chest discomfort), abdominal pain.
The following are less common Tretinoin side effects (occurring in 10-29%) for patients receiving Tretinoin: Weight increase, heart rate irregularities (arrhythmias - see heart problems), flushing, poor appetite, weight loss, earache or feeling of fullness in the ears, diarrhea, dizziness, constipation, numbness and tingling in hands and feet, anxiety, heartburn, low blood pressure, insomnia, depression, high blood pressure, confusion (source).” (4)
Looking at that list of possible symptoms of Retinoid Toxicity - is it clear why it would be good to know if infection or vaccine injured people really need to cut down on carrots/kale/peaches/mango, rather than think of them as a super healthy food for everyone equally? The comments to the post are interesting in that some people have no problems with the Retinoid medication and others reported severe problems and needed more information than they had been receiving. (4)
First do no harm, first requires figuring out what is causing harm to an individual. Brings to mind the old joke - Patient - Doctor it hurts when I do this - demonstrates. Doctor - Well don’t do that.
If you don’t know what is causing a problem, then offering solutions is just guessing based on averages. No single person is an average - an average represents no single individual in the real world. An average is just math. Evidence based medicine is guidance from averages and needs to be viewed that way - a starting point that is fine-tuned based on the individual’s needs. Public health education guidance that is helpful is thorough enough for an individual to sort out which parts seem pertinent to their own symptoms or lifestyle habits or health and family background.
Overview & diet tips: IBS/Inflammatory Bowel Syndrome, Colitis *
*Part of this is from a new section in the Protocol Collation & Therapy Goals.
Stress and autoimmune issues can increase the risk for Irritable Bowel Syndrome (IBS) or Inflammatory bowel conditions including colitis. Whether someone has IBS or colitis is based on severity of weight loss and timing of diarrhea. Immediately or shortly after a meal and no weight loss or minimal may be IBS, while more frequent watery stools even while sleeping and weight loss puts the problem more into the category of colitis.
The same foods can be problems for either condition. TRP channel triggers in our spices and foods and life can activate ion channels and a sudden shift of fluid from the body/cellular interior is expelled in an urgent bowel movement of watery stool.
TRP channel Activators:
Caffeine, cinnamon, mint, horseradish, ginger, turmeric, nutmeg, cloves, black pepper, hot pepper,
Acidity overload - a large lemonade or acidic soda, or tomato dishes, acidic supplements in larger doses, coffee. *buffer with a little tiny dash of baking soda added to the coffee may help but if a severe problem the caffeine would be a trigger too.
Being too hot ~ above 80’F or too cold, below 40’F - example: chilled sock feet on a cement basement floor in the winter leaving the body shifted colder suddenly.
Pressure changes from a gassy meal - more likely with fermented foods, or raw or undercooked vegetables, especially cabbage or cruciferous broccoli and cauliflower, or a large apple or pear, or a big serving of my tapioca pudding - these all promote more growth of our microbiome, which creates gas as a waste product; or carbonated beverages; or external from an amusement park ride or inverted exercise positions in yoga maybe.
Graphic with a list at subsection: TRP Channels - IBS & Migraines, TRP channels may be involved in COPD, CHF, and Preeclampsia.
I made this graphic in 2016 when I had to figure out my own new onset IBS/colitis - it did have weight loss and disorientation from the frequent loss of electrolytes is also a problem. It becomes difficult to keep enough food in long enough to absorb any nutrients. See the post: And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common?, March 30, 2016. *The answer is activators of TRP channels. There seems to be an increased number of TRP channels in the conditions that seem to be worsened by use of the trigger seasonings or activities.
What can help bowel symptoms?
Some of my tapioca pudding with extra tapioca or arrowroot starch. The colon needs short chain fatty acids (SCFAs) from beneficial bacteria converting resistant starch into the SCFAs. Butyrate is an important SCFA made by our microbiome when it is well fed with resistant starches in our diet and adequate zinc. Supplements of butyrate may also help while healing, about 500 mg once or a few times a day.
Sponge like mucilaginous foods are soothing, hold onto water content, and restore the jelly-like coating that lines our gastrointestinal tract.
Oatmeal, bananas, white rice are known to be mild starches that can be tolerated. Psyllium fiber, slippery elm powder, marshmallow root powder, flax meal, Gumbo file, (tapioca and arrowroot starch - not quite the same, similar) are all water soluble mucilaginous fiber sources that get jelly like when mixed in hot water.
Okra is a vegetable that can be soothing and made with a little Gumbo file seems to cut down on veggie related gassiness.
Chia seeds also have water soluble fiber.
See half way down the page: Membranes & Inflammation.
Also post: ACE2, COVID19, & Diarrhea - it gets complicated. March 20, 2020. Diet tips excerpt included next. I got sick early outbreak and was one of the 15% or so who also got bowel symptoms. I got better with my usual strategies of avoiding TRP activators and increasing mucilaginous foods. Avoiding oxalates was also important and that tripped me up off and on until I learned more about those food sources - beans and nuts and coffee and chocolate, sad face. Prepping differently can reduce oxalate load somewhat.
This is the second half of the post that is specifically tips for colitis type bowel symptoms - pain and frequent diarrhea shortly after eating. I found laying down for a half hour after eating could help retain the food longer so some nutrients could be absorbed.
Diet tips that might help inflammatory GI symptoms.
Now, change of topic, what to do about diarrhea and other digestive symptoms? The digestive symptoms may include stomach pain/nausea, vomiting, and intestinal pain after eating, particularly after some types of foods. Inflammatory digestive conditions can be helped by eating foods that are similar to the layer of mucus that lines the intestines during normal health - restore it by providing it in the menu choices.
“The soluble indigestible constituents of plants, called soluble dietary fibre, should be present in a plant-rich diet as well. In this case, water soluble components, such as β-glucan, pectin, fructan, and heteropolysaccharides from gums, mucilages, and hemicelluloses, are predominantly used as carbon sources by the colonic microbiota, particularly by the constitutional lactobacilli and bifidobacteria. A particularly high level of soluble fibre is found in fructan-containing plants, such as asparagus, onion, globe artichoke, and Jerusalem artichoke; as well as in legumes, such as beans, peas, and lentils; and in whole-grain cereals, fruits, diverse seeds, and succulent plants .” (21)
Foods that are mucilaginous – a little sticky and gooey – include:
The vegetable okra and the powdered sassafras leaves used in Creole gumbos known as Gumbo File. I find adding Gumbo file to the cooking liquid reduces gassy digestive effects. The gooey part is the good for your GI tract part.
Slippery Elm Powder is an ingredient in some herbal teas designed for use with a sore throat. Marshmallow Root Powder is very similar in healing benefits and a little less expensive than Slippery Elm Powder (and yes, marshmallows were originally made from Marshmallow Root Powder, now marshmallows are just another corn product).
Gelatin, bone broth, Jello (TM), are all mucilaginous from the collagen/gelatin from animal products. Agar is a vegetarian gelatin substitute made from seaweed and Irish Sea Moss can also be used to make gelatin like desserts. Tapioca starch can also be used to make a gelatin like dessert that is slightly more dense in texture than Jello (TM). The Gumbo File could be used to thicken fruit juice or fruit also for a gelatin dessert like effect but the flavor again might be more noticeable than if Agar, Tapioca Starch or traditional animal derived gelatin were used.
Psyllium Husk powder is a mucilaginous fiber sold as a fiber supplement and stool softener. (21) All of these mucilaginous foods could help with constipation by increasing moisture content of the bowel movement or help with diarrhea by helping absorb water content of the bowel movement as well as by reinforcing the mucus like lining of the intestinal tract.
“In the common diet of the indigenous population in America and Asia, particularly India, Thailand, Puerto Rico, and Mexico, the seeds of chan (Hyptis suaveolens L.), chia (Salvia hispanica L.), or basil (Ocimum basilicum L.), all belonging to the Lamiaceae family, are applied to drinks or food with beneficial health effects.” (21)
Aloe, cactus, Lotus Root, Chinese yams, See: Word of the Day: Mucilage.
Flax meal powder (21) when mixed with boiling water and stirred for two minutes will become mucilaginous and can be used as an egg replacer as it can act as an emulsifier. Gumbo File can also be mixed with boiling water and used in place of eggs as an emulsifier. It has a stronger flavor than flax meal powder but is a finer grind. Golden flax meal is slightly less gritty in texture than regular brown flax meal. Flax seeds are very tough and will not be digestible or chewable unless ground before use.
Egg replacer ratio that I use- to replace 1 eggs ~ 1/4 cup liquid egg (like scrambled egg in a carton, used in some bakeries to save time): 10 tablespoons water (5 ounces), bring to a boil and quickly remove before over-evaporating, stir into a bowl with two-three tablespoons of Golden Flax Meal or Gumbo File. Stir for two minutes until thickened and the flax meal would turn the water from clear into an opaque creamy white color. Gumbo File is greenish and dark, and would be least noticeable in a chocolate brownie type of recipe.
Muffins/vegan quick bread:
I have grown to prefer a combination of the two for best emulsifying power. For larger batches - Wet Ingredients step 1: 3 tablespoons each: golden flax meal and Gumbo file, [and 2 tablespoons ground inner pomegranate peel but the egg replacer effect doesn’t need it], add two cups boiling water (16 ounces) and stir until thickened and opaque (gooey). This is more dilute than the 2 tablespoon version, but I add chopped nuts and dried fruit to soak up some of the liquid, and add less liquid to the recipe if need be.
This batch makes ~ 24 vegan/dense muffins, bake at 350’F for ~25-35 minutes depending on pan choice. Vegan baking is moist and dense - good for resistant starch, less good for light and fluffy baked goods. So mini muffins, brownie pan, and some fibrous texture to help hold moisture and give structure helps - chopped fruit, nuts, shredded coconut or carrot or zucchini can help.
Dry ingredients: 4 cups varied flours, 1/2 cup sweetener, 1 1/2 teaspoons baking soda, 1 teaspoon cardamom, 1/2 rounded teaspoon salt; Wet ingredients: add to the hot emulsifier: 1 cup chopped nuts or sesame seeds, 1 cup chopped dried fruit, 1/2 cup olive/sesame or coconut oil, 1 tablespoon apple cider vinegar, 1 tablespoon vanilla; combine the dry and wet & an additional ~2 cups almond milk, - might be a basic recipe ratio for 24 muffins or a jelly roll pan or 2 cake rectangle pans (used for brownies too).
Insoluble fiber is also needed to add bulk, & Soluble fiber to act like a sponge.
Artichoke hearts/artichoke leaves are a better source of insoluble fiber (thedailymeal) which adds bulk to a bowel movement so it isn’t too watery and helps everything move along a little faster. A diet that has little fiber and more processed foods, refined grains, and meat and dairy products can take many days to pass through, increasing risk of cancer and constipation pain and hemorrhoids.
Jerusalem artichoke, carrot, turnip – (1850) These root vegetables would be a source of soluble and insoluble fiber. Sweet potato and oat bran are also good sources of soluble fiber. (Mucilage/ScienceDirect) Black beans and other beans, nuts, seeds, broccoli, pears, nectarines, apricots, apples, guava, barley, figs, (Top 20 Foods Rich in Soluble Fiber)
Hydrolyzable tannins - pomegranate peel and walnuts (an oxalate source)
Hydrolyzable tannins along with gelatin like foods can also be soothing during a diarrhea illness. (8) They help reduce inflammation by reducing the amount of the inflammatory chemical lipo-polysaccharides. (16) An excessive amount, an overly large serving of hydrolyzable tannins may increase irritation of mucus membranes so the rule holds: dose makes the poison, dose makes the cure. Hydrolyzable tannins are tannins that can bind with water and other molecules and form large complexes.
Condensed tannins don’t bind with water and are even more prevalent in leaves, making up as much as fifty percent of the tannin content within leaves of most plants. (12) Plants tend to make either condensed tannins or hydrolyzable tannins, but not both. The plant makes more in response to hotter sunny summer days, and in response to insect damage – the plant’s protection against cancerous effects of UV light, and a toxin if eaten in quantity by the insects. (17) See the Reference list for a longer list of plant sources of hydrolyzable tannins. (18)
Hydrolyzable tannins may help protect against cancer cells and other damaged or infected cells by promoting apoptosis (9) – the killing and engulfing of debris or a damaged cell by white blood cells. They have antiviral capability. (31) They also act as antioxidants and help reduce levels of oxidative chemicals. (19) Hydrolyzable tannins also act as COXII inhibitors (20) as do other antioxidants (last post).
Tannins are typically found in tea (tea leaves) and other tree leaves such as Sassafras leaves made into Gumbo File or Bay Leaves that are added to a soup broth at the beginning of cooking and removed before serving the food. Condensed tannins don’t bind with water and are even more prevalent in leaves, making up as much as fifty percent of the tannin content within leaves of most plants. (12)
Oak leaves are also a source of tannins, and are traditionally used to “tan” hides – with the tannin rich oak leaves. The initial soaking process with the tannin rich leaves prepares a deer skin so the hair can be scraped off the leather hide more easily – it still is a lot of work to tan a hide in the traditional way. Oak barrels are used in the aging of wine and liquors possibly because of the gradual addition of tannins to the aging alcohol product.
Walnuts also have hydrolyzable tannins and the binding of water and other nutrients is visibly noticeable when walnuts are cooked with sweet potatoes in a casserole – the dish can turn brown in color instead of the pretty orange color of sweet potatoes. It has not turned bad, it has hydrolyzed the tannins. The hydrolyzed tannins bind with other nutrients too and can slightly reduce nutrient availability for absorption out of the intestines , (15), – however if the goal is to heal inflamed and painful intestines than having more nutrients stay in the intestines may be part of the benefit – literally reforming the mucus lining of the GI tract that would be continually lost when severe watery diarrhea is an all day problem.
Walnuts however, are a source of oxalates and an upset bowel condition may also be sensitized to the sharp crystal pain of oxalates that aren’t being broken down properly.
Pomegranate peel is not an oxalate source though the outer peel is so rich in tannins that it is better in a tea or extract than directly used in foods like the inner peel can be used.
A larger quantity of tannins can also be obtained from pomegranate peel. The white inner part of the peel has slightly less than outer peel which makes it less bitter in flavor and less of a diuretic. Tannins have a diuretic effect and a larger serving of pomegranate peel products can have too much of a diuretic effect. I use a vegetable peeler to remove the outer reddish-purplish rind and then I separate the white membrane from the seeds and trim away any bad spots from the white membrane and remove any discolored or spoiled seeds.
The white membrane of the pomegranate peel can be minced and added raw to a salad or added to a soup. In foods that are acidic the color of the membrane and the dish you are preparing will become more reddish in color or might turn brownish if the tannins are hydrolyzing with other ingredients and the water content. In foods that are alkaline the color will turn brown. This is least noticeable in black bean soup, white beans will have a brown broth and greenish split pea soup looks odd (warning – foods are chemistry and this is kind of fun).
The red part of the peel can be used in tea or to make a liquid concentrate that is used in small amounts but it is too bitter to eat and the diuretic properties can be potent – have the extract or tea early in the day and drink plenty of water throughout the day to help it pass through before you hope to sleep through a night.
Why would you bother then?
Pomegranate peel has a long list of medicinal benefits potentially including cancer treatment or prevention. It is antimicrobial, anti-worm, etc, a long list, see this webpage for health benefits, preparation and menu ideas: G13: Pomegranate.
A bean soup recipe using dry beans is the last recipe on page, G8: Cookies and Bean Soup. I usually add 2/4 tablespoons dried/fresh inner peel to my ~ 2 quart batch of soup. Think of it like mincing garlic for the soup - but the pom peel is also good in baked goods. It acts as a preservative and adds to the emulsifiers.
The cookie recipe uses the Golden Flaxmeal as emulsifier with images. I hadn’t known about the Gumbo file when I wrote that page. It also discusses adapting recipes to gluten free flour mixes. Corn flour can be a Leaky Bowel Membrane problem food though, as corn also effects the Tight Junctions between intestinal cells.
Alkalizing Foods - a document about lower inflammatory food choices, with additional sections on inflammatory foods that some but not people may be sensitive too - in a way that is not a “peanut allergy” and lab testable.
Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.
Xu, YL., Ding, CL., Qian, CL. et al. Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice. Cell Death Dis 10, 958 (2019). https://doi.org/10.1038/s41419-019-2186-9 https://www.nature.com/articles/s41419-019-2186-9
Cui-Ling Ding, Chun-Lin Qian, Zhong-Tian Qi, Wen Wang, Identification of retinoid acid induced 16 as a novel androgen receptor target in prostate cancer cells, Molecular and Cellular Endocrinology, Vol 506, 2020, 110745, ISSN 0303-7207, https://doi.org/10.1016/j.mce.2020.110745.
Qian CL, Ding CL, Tang HL, Qi ZT, Wang W. Retinoic acid induced 16 deficiency exacerbates high-fat diet-induced steatohepatitis in mice. Cell Biochem Funct. 2020 Aug;38(6):753-760. doi: 10.1002/cbf.3542. Epub 2020 Apr 14. PMID: 32289885. https://pubmed.ncbi.nlm.nih.gov/32289885/
Reviewed by Marta, Tretinoin and retinoids- toxicity and safety, Feb 26, 2018, truthinaging.com, https://www.truthinaging.com/review/tretinoin-and-retinoids-toxicity-and-safety