This is not medical advice I am posting this for informational and educational purposes.
This is not done I have a lot to add to it but I am kind of burned out. I will finis it later after I take a break.
Gastrointestinal motility and digestive enzymes.
This is mostly on bile but I wanted to cover the other areas of digestion before I covered bile.
Inhibited bile causes constipation. Frequent constipation increases Bilophila Wadsworthia which causes appendicitis. Trans-fats and saturated fats should be avoided when bile is inhibited or when constipated because they increase the growth of Bilophila Wadsworthia. Trans-fats should be avoided anyways they are very bad for our health.
Most know how digestion works but we need a refresher. When we chew our food it is mixed with saliva which has some digestive enzymes in it. When we swallow it is propelled down the esophogus where it is mixed with enzymes and gastric acid. The end result is called chyme. The chyme is pushed into the small intestine (duodenum). Many will ask me how to increase bile production but doing so could cause more harm then good. The problem causing the inhibited bile flow needs to be addressed. For example a dam can only hold so much water. If there is more water then the dam can hold it will flood over the top. Adding more water to the dam adds to the problems and could break the dam. When there is a blockage causing bile flow to be inhibited then increasing bile would be like adding water to a dam that is already overflowing. Most health issues mentioned in this article I have discussed elsewhere on my blog.
Peristalsis is the movement of food through the digestive system. It is the cause of the gurgling sound you hear when you are hungry or digesting food. Usually you cannot hear it. I do not know why but I and my friends experienced this. As we healed our digestive system you could feel the food moving and the sounds of digestions were very loud. As we healed they became quieter and quieter.
In the small intestine the food is combined with bile and pancreatic enzymes to break it down further and for nutrient absorption. The smooth muscle in the intestines are ring shaped and alternate between contracting and relaxing. This causes the food to move slow enough through the digestive tract for it to be broke down and for the nutrients to be absorbed. The neurons are stimulated by acetylcholine, and substance P to get them to contract. Nitric oxide, vasoactive peptide and ATP relax the muscles. This causes a motion that moves the food through the digestive tract and occurs the most in the small intestine. There are health issues that can cause a high acetylcholine and high substance P levels. High noradrenaline reduces substance P which can interfere with intestinal motility and can lead to constipation. High estrogen levels can inhibit substance P. High substance P levels can cause inflammation and lead to inflammatory bowel disease. There are health issues that can cause low acetylcholine and low serotonin levels. This also will cause a loss of motility leading to constipation. An imbalance in our immune system can cause bile flow to be inhibited. Estrogen inhibits bile flow and progesterone pormotes bile flow. This causes the liver and thyroids to become sluggish. This can also lead to interstitial cystitis. All the above mentioned things can inhibit receptors and throw hormones out of balance. If not addressed it will become chronic and start a cycle that is difficult to break and can take months to years to heal from.
If the gurgling in the gut is excessive and there is cramping, abdominal pain, and possibly nausea and vomiting it could indicate slow gut motility or a blockage. This can be caused by intestinal damage, hormone imbalance, inflammation in the intestines, dysbiosis, candida overgrowth, a deficiency in certain gut microbiota, slow or inhibited bile. This causes gas, bloating, and distention (inflammation in the gut). If we have a T cell imbalance or high B cell levels this can also cause it. If not addressed it can result in a decline of intestinal health our the health of the body. High histamines can cause inflammation that can cause blockage. We do not want to inhibit them because histamines are needed to stimulate gastric acid. It is best to work on reducing them.
If the digestive system is injured and we do not give it the things needed for it to heal then it loses the ability to sense nutrients and food that has entered it so it cannot respond to them. The longer it goes like this the worse it gets and the longer it will take to heal.
Bile acid is needed for the healthy brown fat to be produced. Bile acid is synthesized form cholesterol. Excess oxidative stress or inflammation in the liver can cause low cholesterol levels or can inhibit it’s production which would prevent the bodies ability to produce bile properly. This can also cause bile to become inhibited. When this happens bile production is reduced and it becomes thick. Phosphatydylcholine is needed to store bile in the gallbladder. I have found most who have problems with choline metabolism have benefited from sunflower seed oil. Excess oxidative stress can cause methionine and choline to become depleted. This inhibits the bodies ability to produce bile.
If you are deficient in certain enzymes often times there are plants you can consume that will helps digest foods that require those enzymes.
Lactase- (B-Galactosidase)- deficiency causes lactose intolerance. It breaks down Lactose down to glucose and galactose. Damage in the gut can cause it to not be reabsorbed. If this happens the gut microbiome will break it down causing gas and bloating. Those who are lactose intolerance will usually also be intolerant of FODMAPS until they get their gut healed enough to correct the malabsorption issues. Those who have malabsorption issues may benefit from taking Lactase when consuming dairy products. Saccharmyces Boulardii has been found to increase enzyme function in those with Lactose and FODMAP intolerance. If a person is lactose intolerant if they avoid dairy products while supplementing galactooligosaccaride for about a month, it has been found to increase Lactose metabolizing bacteria which prevents the bloating and ill effects of lactose. Also slowly introducing dairy into the diet a little at a time can increase the gut microbes that produce lactase. That would prevent a reaction to lactose also.
Alpha-galactosidase- helps break down digested fats and saccharides a deficiency causes lysosomal storage diseases. If defficient in Alpha-Galactosidase when eating fiber and high sulfur foods a person will develop gas and bloating. Those who have a deficiency in Alpha-galcatosidase will be intolerant to complex carbohydrates and may be intolerant to gluten. Beans will be a problem for a person lacking this. Infection can cause A-gal to be inhibited from the LPS produced. Inducing autophagy can testore A-gal. Tick born illness can cause autoimmune disease that can cause the body to make antibodies against a-gal. Balancing the immune system is very important. If not addressed it can lead to a sensitivity to meat.
Things that help with lysosomal storage disease should help with this. https://iamajuicer.wordpress.com/2018/08/21/things-that-may-help-with-lysosomals-storage-disease/
Sucrase- secreted in the small intestine. Catalyzes sucrose , fructose, and maltose. A deficiency will cause lactose intolerance, gas , bloating and diarrhea when things containing sucrose are consumed. Inflammation can cause it’s excretion into the small intestine to be inhibited. Sucrase is also known as invertase. Thyroid hormones and corticosterone stimulate sucrase and maltase. Inflammation and intestinal damage will decrease it’s secretion. High CD8 T cell levels inhibit Sucrase. I have posted on balancing T cells.
Amylases-work with other enzymes to break down polysaccharides. It is the major form of amylase found in humans and breaks down starch to maltose and dextran. It prevents bacteria from producing biofilms by breaking them down. It is secreted in saliva and from the pancreas.
endopeptidase (enterokinase) that breaks down proteins into smaller peptides (it is a protease) It is produced in the stomach and is one of the main digestive enzymes. It transforms trypsinogn into trypsin. procarboxypeptidase into the active enzyme carboxypeptidase which is involved in the maturation of proteins produced. Carboxypeptidase is also involved in enzyme and hormone production throughtout the body. It is produced in the mucus membrane showing the importance of restoring the health of the mucous membrane. This can result in protein and enzyme deficiencies in the body.
Trypsinogen- is the precursor form of trypsin it is found in pancreatic juice that is released in the small intestine. Trypsinogen is activated by the protease enteropeptidase which is produce by the mucus of the duodenum. Trypsin breaks down proteins to ammino acids.
Chymotrypsinogen- precursor for chymotrypsin. It is activated by trypsin.
Pancreatic Lipase- It is secreted into the small intestine in it’s completed form. But it only becomes effective in the presence of colipase which is a co-enzyme.
Phospholipase-converts lipids(fats) to phospholipids.
Lipase-breaks down triglycerides to fatty acids and glycerol. Deficiency causes a lack of fats needed by the body and fats in stools. Lipase also protect the body from parasites and pathogens. If deficienct a person will suffer from malabsorption. There are microbe derived lipases that have been shown to be effective for Lipase deficiency.
Na+ Taurocholate Cotransporting Polypeptide (NTCP) is used by the liver to extract BA returning to the lever through the portal vein. Should not be stimulated in those with cholestasis it can damage the liver. A deficiency causes muscle weakness. If it is inhbited bile salts can build up in the liver resulting in liver damage. This also results in an increase in blood levels of bile acids.
Pancreatic Polypeptide self-regulates pancreatic secretion activities. It’s secretion is increased from protein consumption, fasting, exercise, and is decreased by glucose and somatostatin. It can inhibit gallblader contractions and pancreatic exocrine secretion.
Pancreatic Elastase – help finish breaking down foods. If there is excess oxidative stress , inflammation or immune imbalance that effects the pancreas it can inhibit pancreatic enzyme secretion. They usually test for this enzyme in stool to see if the pancreas is functioning properly.
Most of these hormones are effected by our brain especially the hypothalamus. If we have endotonins, heavy metals , glyphosate or other toxins that effect the brain then our digestion will be effected which further effects our brains. The hormone imbalance causes mental issues. They can be corrected if you address what is causing the imbalance. Many will take medications, which only treat the symptoms. Most medications for those types of things effect digestive hormones adding to the problem. Then when a person starts correcting the problem their mental issues become worse because of the drugs they are taking and the body starting to function correctly will swing hormones in the other direction. When the digestive system is damaged our cells that produce hormones become less numerous. We must try and protect the so healing can begin. Also nerve cells become less numerous which makes our bodies digestive responses to be much lower. Regular and electric acupuncture have been shown to help restore normal hormone levels. Bile acid also regulates lipid and glucose homeostasis. If bile acid become inhibited Thyroxine (T4) levels increase and Tiiodothyronine (T3). Low T3 levels inhibits oxidation which is needed to use lipids and cholesterol in the body. This will cause low LDL levels and high HDL level. Low T3 levels inhibits the bodies ability to synthesize proteins. Insulin loses it’s ability to inhibit glucogenesis. This cause glycolysis to be inhibited. This also effects the heart and can cause heart palpitations. High T4 levels can cause a decrease in serotonin.
Ampulla of Vater blocakge– inflammation, oxalates, toxins, infection or damage in the body can lead to pancreatic enzymes building up causing the pancreas to digest itself.
If you have blockage inhibiting enzyme secretion I would not advice stimulating the secretion until the health problems causing the blockage have been addressed.
When we have metabolic issues, inflammation or any other of the health issues I have describe these enzymes can be effected. Especially if we have damage to our digestive system.
Serotonin – (5-HT) regulates gut motility. It is produced in the mucosa of the gut. It increases peristalsis (movement of food through digestive tract). It has been found to be low in those with inflammatory bowel diseases. A deficiency can cause gastroparisis and bile reflux. It also stimulates adenylyl cyclase which is involved in cell signaling throughout the body. Most drug agonist of the 5-HT receptors damage the liver and heart. Acupunture stimulates serotonin. There are some disorders which inhibits 5-HT from exiting the cells. This causes a build up in the cells and a person will be senstitive to 5-HT but would still have symptoms of 5-HT deficiency.
Motilin – triggered by fasting, and fatty foods. Controls peristalsis by stimulating smooth muscle contraction and relaxation to coordinate the movement of food through the digestive tract. The antibiotic erthromycin stimulates motilin. Motilin had been found to be low in those with inflammatory bowel diseases. Acupuncture increases motilin. Motilins effects are influenced by PH. Low PH motilin inhibits gastric motility at higher PH it stimulates gastrointestinal motility. Food intake slows the production of motilin. Insulin also inhibits the secretion of motilin.
Reflux can be cause by bile issues in two ways. If there is a blockage a person could experience bile acid reflux. If there is insufficient bile production the the acid from the chyme does not get neutralized by the bile and will cause acid reflux. L-taurine and betaine also known as TMG helps with bile production. Cysteine is also needed and taking NAC (N-acetylcysteine) about three times a week has been found to help. If it is taken more then that the benefits are lost.
Gastric Inhibitory Peptide – triggered by glucose and fatty foods. Decreases gastric emptying and stimulates the release of insulin. It promotes fat storage.
Vasoactive Peptide – increases blood flow to the gut, supplies eleyctrolytes to pancreatic enzymes and bile.
Guanylin – causes secretion of chloride , decreases absorption of water from the gut. It prevents the sodium levels from the body from getting too high by inhibiting salt absorption and by stimulating the secretion of bicarbonate and chloride.
Glucagon – glucagon supresses CYP7A1 which reduces bile production. This can lead to insulin resistance and glucose intolerance. Glucagon prevents blood sugar levels from getting too low. It is involved in gluconeogenesis which produces glucose form proteins.Glucagon also breaks down fat stores in the blood stream. Excess glucagon leads to diabetes and thrombosis.
Glucagon Like Protein-1 (GLP-1) Whey protein increases GLP-1, glucose also stimulates GLP-1. Slows down digestion. It increases the size and health of pancreatic B cells. Stimulates brain repair. It’s release is stimulated by TGR-5. GLP-1 is involved in appetite suppression and glucose homeostasis. Low levels causes glucose deficiency. Carbohydrates and elevated blood levels of proteins helps stimulate glucagon . If we are deficient in glucagon glycogen can build up in the livers. It brings down glycogen in the liver by breaking it down to produce glucose. Somatostatin inhibits glucagon production. Excess glucagon cause weight loss and deficiency causes weight gain. Fasting stimulates glucagon production.
Secretin- helps regulate water homeostasis in the body, helps regulate the PH of the small intestine by gastric acid. Secretin inhibits gastic acid production and stimulates the production of bicarbonate. Secretin also stimulates bile production. It is produced mainly in the mucosa of the small intestine and jejunum. It is release from the low ph caused by chyme entering the small intestine.
Secretin deficiency causes a loss of neural progenitor cells. Progenitor cells are similar to stem cells. Since secretin increases neural progenitor cells it helps with autism, motor coordination and improves memory. Secretin helps with asthma by acting as a bronchorelaxer. Secretin reduces symptoms of pancreatitits.
In order to function properly levels of cholecystokinin and insulin need to be normal. If they are dis-regulated it effects secretin levels. It also stimulates polyamines in the pancrease which is needed for cell growth. Polyamines also regulate ion channels including the NMDA recemptors, AMPA receptors and potassium channels. Excess polyamines can cause the blood brain barrier to become more porous. Showing the importance of secretin homeostasis. When H Pylori in in it’s pathogenic form it will cause a secretin deficiency. Secretin promotes the production of mucus. A decrease in secretin decreases the function of angiotensin 2. Secretin increases thirst. Secretin increases the feel good hormone oxytocin.
Now the bad if a person has bile blockage like cholestasis it can cause liver damage. I discuss things that can help with that at the end of this blog post. Secretin causes Zollinger-Ellison syndrome to worsen.
High levels of somatostatin inhibits secretin.
Cholecystokinin- stimulates the release of digestive enzymes and bile from the pancrease and bladder. Whey protein stimulates CCK. Fat intake also stimulates CCK. A deficiency in CCK causes malabsorption and can lead to Type 1 diabetes. Damage to the mucus membrane can cause a deficiency. This can also be caused by autoimmunity. This is where a dilemma occurs. High levels of bacteroidetes or high levels of methane producing bacteria can inhibit CCK. Protein stimulates CCK. I believe working on bile blockage and then once that is corrected increasing bile flow first to reduce the bacteroidetes levels and methane producing bacteria then adding protein into the diet once they are reduced would most likely correct the problem along with restoring the health of the mucus membrane.
Intrinsic Factor-important in the absorption of vitamin B12. Often times B12 deficiency is caused by a lack of the microbiota that produce B12 but is mistakenly attributed to and intrinsic factor deficiency.
Haptocorin-binds to B12 in our food protecting it from our gastric acid so it can survive the stomach. It is found in our saliva. This shows the importance of making sure we chew our food very well.
Gastrin- hormone that stimulates gastric acid secretion. It is released from the pariental cells in the stomach. It also aids in gastric motility. Elevated gastrin can cause hypergastrinaemia. Low levels can cause hypergstrinaemia. Infection can effect gastrin levels and so can histamines. Histamines are needed for Gastrin stimulation if histamine levels are too low the we will not produce enough stomach acid. If they are too high then we can get acid reflux. If someone is not producing enough acid then they most likely have low histamines and would benefit from fermented foods and aged meats which are high histamine.
Gastric inhibitory polypeptide- an inhibiting hormone of the secretin family. It stimulates insulin secretions based on how much glucose is present. It stimulates glucagon secretion and fat accumulation. It is found in intestinal mucus, small intestine, and jejunum of the gastrointestinal tract. Has many other functions throughout the body including bone growth.
Vasoactive intestinal peptide- serves functions throughout the body but relaxes smooth muscles in the trachea, gall bladder and stomach.
Bombesin- stimulates gastrin release from the pancrease. It also stimulates adrenal and pituitary hormones. It increases the thickness of the mucus membrane. It modulates the neural firing rate in the intestines so is involved with gastrointestinal motility.
Somatostatin reduces histamines which will reduce the gastric acid stimulating effects of histamine. In those with inflammatory bowel issues somatostatin in usually very high. Acupuncture has been shown to reduce somatostatin. Most lactobacillus bacteria will reduce somatostatin. Somatostatin prevents the over production of certain hormones in the body. If there is excess somatistatin it will inhibit hormones especially insulin. Somatostatin inhibits glucose and fat absorption. It inhibits insulin and glucagon in the liver. It stimulates muscle contractions in the intestines speedingup transit times. Protein stimulates somatostatin.
Cholecystokinin, glucagon-like-peptide, gastrin-releasing peptide stimulate somatostatin.
Substance P, insulin, pancreatic polypeptide, and opioids inhibit somatostatin.
Excess somatostatin inhibits bone growth, disrupts sleep, and increases dopamine, norepinephrin and epinephrine.
High levels somatostatin will cause high thyroid hormone levels because it inhibits thyroid stimulating hormone which senses hormone levels and shuts them down if they get too high. This causes weight loss no matter how much a person consumes , flushing or hot flashes, and heart palpitations.
Insulin- breaks down blood glucose. Excess insulin can lead to cancer and many other health problems. Glycoproteins increase insulin. Whey protein increases insulin and reduces blood glucose levels. This is one that confuses me and makes me believe those with inflammatory bile have blockages. Many with inflammatory bowel have high insulin levels which stimulates CYP7A1 which should increase bile production and still they have low bile flow and often times CYP7A1 levels are low. It may be that inflammation is inhibiting the receptor.
Ghrelin-triggered during hunger or calorie restriction. Stimulates appetite. Whey proteins increases Ghrelin. Ghrelin is involved with gastric emptying.
Deacyl-ghrelin – DAG decreases gastric emptying, induces postprandial fullness and improves insulin sensitivity.
Peptide YY- secreted after eating it cancels out the effects of ghrelin.
Pheonixin – expressed in the hypothalamus, it stimulates appetite.
Peptide YY- produced in the gut where short chain fatty acids are produced. Proprionate and butyrate increase expression of Peptide YY. It reduces appetite. It is stimulated from the consumption of fiber from fruits and vegetagles. It also reduces pancreatic secretion.
Leptin – regulates body fat.
Bile stimulates the secretion of electrolytes and water into the intestines which stimulates digestion. Biles acid stimulates the release of 5-HT. Those with inflammatory bowel diseases have been found to have high levels of bile acids Taurocholic Lithocholic Acid, Taurocholic acid and Taurocholic Deoxycholate.
Bile acid promotes liver regeneration by activiating BA recperors Farnesoid X receptor and G-Protein-coupled BA receptor1 (GPBAR1 or TGR5) . This shows the importance of bile acid homeostasis. Proper bile acid production is very important for maintaining a balanced gut microbiome.
Inhibited bile can cause gall stones and lead to liver and kidney disease.
There are many things that can inhibit bile production. Inflammation, toxins, metabolic issues, especially inhibited receptors involved with bile production. Infections can cause bile to become inhibited and so can the endotoxins they produce. If we develop leaky gut the LPS (lipopolysaccharide) which is produced by pathogens and our commensals can enter the blood stream. Our microbiome uses LPS to communicate with our bodies but when it gets into the blood stream it causes the same problems a pathogen would. We also have commensal microbes that break down LPS antibiotics and farm chemicals especially glyphosate and glufonisate can kill our gut microbiome. They modulate most organs in our bodies including our brains. They even modulate some of our genes. Without them we will not have an immune system and we cannot restore the body to homeostasis. Metabolic issues can cause acidosis or alkalosis which will also interfere with the propper function of our organs and causes a lot of damage which progresses and becomes more severe if the problems causing them are not addressed. Infection can also change the PH of the body. There is a myth that alkalizing the body will make us healthier. This is not true but it promotes things that are usually commensal like Candida and H Pylori to turn pathogenic. If a person has candida and H Pylori problems they most likely have high ammonia levels. This causes BH4 to become depleted increasing the ammonia levels even more. If not addressed they will start having problems eating high protein foods and high sulfur foods. Another thing that can cause blockage that effects bile flow is oxalates. They can be produced endogenously or we can get them exogenously. If we have leaky gut oxalates that are usually excreted in our feces can easily enter our blood stream. Also many will consume a lot of raw greens. Spinach and Kale are very high oxalate and can increase oxalates in the body. We have oxalate degrading microbiota and if antibiotics or farm chemicals in our food kills them our oxalate levels can indrease. I have posted on my blog on how to deal with those issues.
Bile, an aqueous solution produced and secreted by the liver, consists mainly of bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes, and water.The liver cells are mostly hepatocytes. Bile travels through the liver in a series of ducts, eventually exiting through the common hepatic duct. Bile flows through this duct into the gallbladder where it is concentrated and stored. When stimulated by the hormone cholecystokinin (CCK), the gallbladder contracts, pushing bile through the cystic duct and into the common bile duct. CCK is usually deficient in those with inflammatory bowel disease. Cholecystokinin is released after a meal is consumed. It is stimulated by the production of stomach acid. It is secreted along with secretin. Secretin stimulates bicarbonate in response to the acid from the chyme that enters the small intestin, and It stimulates pancreatic enzymes and forces bile into the small intestine. If we do not produce enough stomach acid then Cholecystokinin is not released and our food will sit in our stomach and ferment. This causes and increase of either methane producing bacteria or sulfur digesting bacteria. Methane and sulfur digesting bacteria cause lower motility in the intestines slowly digestion even more. Bile is needed to stimulate the Vitamin D Receptor.
Simultaneously, the sphincter of Oddi relaxes, permitting bile to enter the duodenal lumen. Lumen is the space in a tubular shape. The hormone secretin also plays an important role in the flow of bile into the small intestine. By stimulating biliary and pancreatic ductular cells to secrete bicarbonate and water in response to the presence of acid in the duodenum, secretin effectively expands the volume of bile entering the duodenum. In the small intestine, bile acids facilitates lipid digestion and absorption. Bile is needed to absorb many nutrients especially lipid (fat) soluble vitamins like Vitamin D, Vitamin E, , Vitamin A and Vitamin K. Only approximately 5% of these bile acids are eventually excreted. The majority of bile acids are efficiently reabsorbed from the ileum, secreted into the portal venous system, and returned to the liver in a process known as enterohepatic recirculation. Ileum is the final section of the small intestine.
If bile becomes inhibited it inhibits the vitamin D receptor further inhibiting bile production and adding to the problem because cholesterol production and conversion becomes inhibited. This will make bile become sludgy leading to low bile flow which will increase estrogen levels and cause high unbound copper levels in the blood. Bitter herbs increase bile flow but the vitamin D receptor has to be addressed along with balancing the microbiome in the gut and healing the intestinal tract. Inflammation needs to be reduced , and prevent thrombosis. There are many things that can block the portal vein. The above mentioned things and also thrombosis can cause it. Thrombosis is blood clotting.
This is why I often times recommend grape seed extract and bacopa to people. It prevents thrombosis. Inflammation because endotoxins can cause thrombosis. Grape seed extract and bacopa reduce inflammation and prevent thrombosis. If thrombosis occurs in the portal vein it will effect the liver, pancrease, and digestive system. This causes pain in the stomach, bloating, inflammation, pancreatic pain, pain in the gallbladder. This can lead to death. Bile flow will become inhibited speeding up the progression of portal vein thrombosis. Those with hepatitis need to use hawthorne or something else. Resveratrol activates hepatitis.
portal vein thrombosis
gastrointestinal symptoms (ex: abdominal pain, nausea, vomiting, and diarrhea), fever and constitutional symptoms (ex: fatigue, malaise, and anorexia/weight loss) . We can also find hepatomegaly with elevated liver enzymes and jaundice , when associated with liver abscess or cholangitis . Laboratory tests usually demonstrate elevated markers of inflammation 
If not addressed in time it can lead to portal hypertension. This results in brain swelling, abdominal swelling . Confusion, anemia and low white blood cell count.
How Bile is Formed.
Bile is produced by hepatocytes, which is then modified by the cholangiocytes lining the bile ducts. The production and secretion of bile require active transport systems within hepatocytes and cholangiocytes in addition to a structurally and functionally intact biliary tree. If this becomes blocked by stones from poor bile production, oxalates or infection a person can develop choledocholithiasis. This will cause problems with the gall bladder, liver, kidneys and digestion. This can also lead pancreatic problems. The symptoms are upper abdominal pain, nausea and vomiting.
Initially, hepatocytes produce bile by secreting conjugated bilirubin, bile salts, cholesterol, phospholipids, proteins, ions, and water into their canaliculi (thin tubules between adjacent hepatocytes that eventually join to form bile ducts). Unconjugated bile is when heme is released during red blood cell break down, the remainder is converted to unconjugated hemoglobin. This form of bilirubin travels from the blood stream to the liver. If the liver cannot convert unconjugated to conjugated it will build up in the blood and a person will develop a yellow like glow. It is normally excreted through the intestines. If there is a rapid destruction of blood cells this can also happen. Infections, toxins, excess vitmin C and excess iron can cause the red blood cells to break down. Conjugated bilirubin is water soluble and if there is a blockage it will be excreted in the urine. Testing for high bilirubin in the urine can help identify blockage.
The canalicular membrane of the hepatocyte is the main bile secretory apparatus which contains the intracellular organelles, the cytoskeleton of the hepatocyte and carrier proteins. Fluctuations in cytosolic and organelle Ca2+ following glucagon or epinephrine stimulation play a major role in hepatic control of glucose production, bile fluid movement and excretion, fatty acid, amino acid and xenobiotic metabolism, protein synthesis and secretion, cell cycle and cell proliferation, among other functions. I discussed in some of my other post about autophagy. It can help issues like this.
The carrier proteins in the canalicular membrane transport bile acid and ions. Transporter proteins found within the canalicular membrane use energy to secrete molecules into bile against concentration gradients. The citric acid cycle is involved in providing the energy for this to occur. Mitochondrial disfunction and a loss of ATP can also interfere with this process. If this occurs cholestasis can occur causing a backup of bile and it can enter the blood stream. If the problem causing the obstruction is not addressed it can lead to fibrosis and vanishing bile duct syndrome. Symptoms are frequent itchy skin, elevated triglycerides, fat growths that appear under the skin. Drugs are often times the cause especially fluorquinolones.
Through this active transport, osmotic and electrochemical gradients are formed. When conjugated bile salts enter the canaliculus, water follows by osmosis. The electrochemical gradient allows for the passive diffusion of inorganic ions such as sodium. The most significant promoter of bile formation is the passage of conjugated bile salts into the biliary canaliculus. The total bile flow in a day is approximately 600 ml, of which 75% is derived from the hepatocyte, and 25% is from the cholangiocytes. Approximately half of the hepatocyte component of bile flow (about 225 ml per day) is bile salt-dependent and the remaining half bile salt independent. Bile Salts are formed in the body by combining bile acids and alcohol sulfates. Bile acid is combined with glycine or taurine to form bile salts. This is a good article explaining how to increase bile salts and the benefits of doing so. Taurine has been found to increase sulfur digesting bacteria which would increase H2S which can inhibit bile production. The is most likely why the western diet causes health problems it is high in taurine.
Osmotically active solutes such as glutathione and bicarbonate promote bile salt independent bile flow. Canaliculi empty bile into ductules or cholangioles or canals of Hering. The ductules connect with interlobular bile ducts, which are accompanied by branches of the portal vein and hepatic artery forming portal triads. Bile is subsequently modified by ductular epithelial cells as it passes through the biliary tree. These cells, known as cholangiocytes, dilute and alkalinize the bile through hormone-regulated absorptive and secretory processes. The hormones are scecretin, acetycholine, ATP, and bombesin. So you can see the importance of making sure we address any issues we have that can inhibit acetylcholine production or cause ATP to become depleted. Issues with glycolysis can cause a loss of ATP. I do not know much about increasing ATP except that creatine helps increase ATP production.
The cholangiocytes have receptors which modulate the bicarbonate-rich ductular bile flow, which is regulated by hormones. These receptors include receptors for secretin which regulates water homeostasis, somatostatin decreases stomach acid production, cystic fibrosis transmembrane conductance Regulator (CFTR) not sure how to describe this one. It is kind of an ion channel/ABC transporter and chloride-bicarbonate exchanger this is where electrolytes are important. These are listed in order of importance sodium, calcium, magnesium and postassium .
For example, when secretin stimulates receptors in the cholangiocyte, a cascade is initiated which activates the CFTR chloride channel and allows the exchange of bicarbonate for chloride. In contrast, somatostatin inhibits the cAMP synthesis within the cholangiocytes causing the opposite effect. While bombesin, vasoactive intestinal polypeptide, acetylcholine, and secretin enhances bile flow, somatostatin, gastrin, insulin, and endothelin (endothelin are involved in electrolyte homeostasis) inhibit the flow. I do not have enough experience with reducing insulin levels and had to have a friend help me with that on facebook. Some metabolic disorders can cause low glucose levels and high insulin levels. It can be corrected but takes someone who is knowledgeable.
Bile Acids Cholesterol catabolism by hepatocytes results in the synthesis of the 2 major primary bile acids, cholic acid, and chenodeoxycholic acid. This process involves multiple steps, with cholesterol 7alpha-hydroxylase (CYP7A1) acting as the rate-limiting enzyme. It is effected by steroid hormones, inflammatory cytokines, insulin and growth factors.
Primary bile acids undergo dehydroxylation by bacteria in the small intestine, forming the secondary bile acids deoxycholic acid and lithocholic acid, respectively. Deoxycholic acid breaks down fats. High protein diet increases deoxycholic acid. Excess lithocholic acid speeds up aging and is carcinogenic. Eating lost of fiber reduces lithocholic acid. Artichoke reduces lithocholic acid and stimulates bile production. If the vitamin D receptor is inhibited then lithocholic acid cannot be detoxed by the body.
Both primary and secondary bile acids are conjugated by the liver with an amino acid, either glycine or taurine. Conjugated bile acids are known as bile salts. Bile salts inhibit cholesterol 7alpha-hydroxylase (CYP7A1) , decreasing the synthesis of bile acids. Despite the increased water solubility of bile salts, they are amphipathic molecules overall (has both hydrophobic and hydropholic molecules). This critical property allows them to effectively emulsify lipids and form micelles with the products of lipid digestion. The bile acid pool is maintained via mainly the enterohepatic circulation and to a small extent (about 5%) by hepatic synthesis of bile acids, as long as the daily fecal loss of bile acids do not exceed 20% of the pool. Micelles help with fat absorption.
Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase. When the digestive system is healthy bile gets easily reabsorbed.
Chenodeoxy cholic Acid and Cholic Acid are the primary bile acids produced. From Chenodeoxy cholic Acid many other bile acids are produced.
Bile acid gets reabsorbed and returned to the liver to be recycled. There are secondary bile acids produced in our digestive tract by our gut bacteria. Our microbiome deconjugates bile. Deoxcycholic Acid is a secondary bile acid produced by our microbiome. It is recycled by the body and is conjugated with glycine or taurine and circulated with primary bile acids. It constitutes about 20% of biles acids.
Lithocholic Acid is a secondary bile acid. It is conjugated with glycine or taurine and sulfated producing sulfolithocholylglycine or sulfolithocholyltaurine. Lithocholic Acid is toxic and can destroy the liver. Sulfation is an important part of detoxing deconjugated bile acids. Sulfation of bile acids decreases their absorption rate which prevent them from reentering the liver so when sulfation is functioning properly then the body can easily detox the toxic bile. Sulfation can become inhibited by metabolic issues, high sulfur digesting bacteria raising hydrogen sulfide and sulfide levels in the body. If there are problems with the CBS or BH4 pathways sulfation can be effected. The SULT genes are effected by our hormones. A change in our gut bacteria, toxins, glyphosate, vaccine injury, infections, leaky gut and many other things can change our hormone levels. This can inhibit the ability for the liver to sulfate bile acids. The pregnane X receptor also know as the xenobiotic sensing nuclear receptor has been found to be inhibited in those with bile blockage disorders. Inhibited PXR can inhibit SULT genes. Those with upregulated PXR have been found to be protected from the negative effects of LCA. Constitutive Androstane Receptor (CAR) is involved in sensing and removing endobiotic, and xenobiotic substances. It detoxes foreign substances and drugs. It has be found to protect form LCA when upregulated by inducing SULT genes. CAR is also involved in energy homeostasis. Fasting can induce CAR. Vitamin D receptor, Liver X receptor, and Farnesoid X receptor are also involved in sulfation and upregulation hve been found to protect from LCA. Most of those receptors have been found to be inhibited in those with bile blockage. Showing the importance of supporting their proper function.
When there is an obstruction biles acid can spill over into the blood stream through OST a and b transporters and also can enter the blood through Multidrug Resistance-associated proteins M1M3,M4 and M6. When there is an obstruction urinary excretion of bile is the primary route of bile removal. If this continues for an extended period of time it can lead to bladder irritation from the caustic effects of the bile acid to the bladder. Constipation form inhibited bile flow is common in interstitial cystitis. This can also take place through the organic acisd transporter.
This is an interesting article on bile acid blockage. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1105662
When Lithocholic Acid cannot be sulfated it remains toxic. Lithocholic Acid is highly carcinogenic and causes cancer. High Lithocholic Acid levels inhibits cortisone production this can cause many health issues including chronic fatigue.
Cellulose has been found to increase the mucus membrane which improves bile flow.
Not sure where to go with this information but took note of it. High nitrogen levels increases bile acid oxidation, high hydrogen levels inhibits bile acid oxidation.
Medium Chain Fatty Acids stimulate bile production which decreases bacteroides and actinobacteria which has been found to be high in those with dysbiosis and inflammatory bowel disease. Low bile acid production increases levels of microbes that produce potent LPS. Tempo a product made from fermented soy has been shown to reduce bacteriodes and inhibit our microbes ability to produce bile salt hydroxolase which inhibits FXR receptor. By decreasing our microbes bile salt hydrolase bile production is restore which reduces the bacteria that inhibit bile flow. If you try this route you would want to use organic because the BT-Toxin and glyphosate found in soy products destroy the gut and alter our gut microbiome causing an increase in microbiota that have a negative impact on our health. The FXR receptor is responsible for homeostasis throughout the body. If the FXR receptor is inhibited a person will develop diabetes, dislipademia, cancer, metabolic disorders, atherosclerosis and renal diseases.
If a person has cholestasis stimulating bile will damage the liver and cause excess bile to enter the blood causing many other health problems. If a person has cholestasis they should not stimulate bile production. Elevated bile production is a sign and symptom of sepsis which indicates cholestasis.
Things that can cause cholestasis is drugs, infection, metabolic issues, gene issues, gut dysbiosis,inflammatory bowel diseases,hormone imblance, T cell imbalcance, excessive inflammation, toxins and many other things. If a person has cholestasis they will have dark colored urine and light colored stools. Pain in the abdomine, excessive itching, fatigue and nausea. In more severe cases the skin and eyes my get a yellow color.
You have to address the cause of cholestasis if it is drug induced then you may have to discontinue the use of the drug, address infection and inflammation, correct metabolic issues and gene issues. Work on reducing gall stones and oxalate stones.
Some things found to help with bile blockage. Gaur Gum, milk thistle, dandelion, vitamin K, Vit D, Calcium but we must make sure we get the right type, sunflower seed lecithen, antioxidants but do not over use homeostasis is the goal. We need some oxidative stress if we completely disable ROS we will defeat the purpose. Radishes have been shown to help with bile blockage. Cod liver oil helps with bile blockage, medium chain fatty acids help with bile blockage, curcumin helps with bile blockage but after a while it should be pulsed because it chelates iron from the body and can cause anemia. Activated charcoal helps with cholestasis but should not be taken close to meals or we will lose nutrients. Soaking in epsom salt and then getting far infrared, sunlight or halogen light gives us magnesium sulfate which helps with cholestasis. If it is caused by gall stones apple juice and apple cider vinegar has been found to reduce gall stones. Lemon juice has been found to reduce gall stones. I had to put lemon juice in water because straight lemon juice was to strong for me and made my stomach hurt. Artichoke has been found to reduce gall stones. We need a variety in our diets, eating poorly can cause bile stones. The more processed foods we eat the better our chances of getting them are. Losing weight too quickly can also cause gall stones. Low HDL levels can cause gall stones that can be caused by hormone imbalances especially high estrogen levels. Citrus fruits reduce gall stones especially the white part of the fruit. Rosemary has been shown to reduce gall stones. Pear juice has also been found to dissolve gall stones. Beet root, carrots and cucumber has been found to reduce gall stones. Drinking excess amounts of soda pop and consuming excess amount of processed sugar can cause gall stones and oxalate stones.
Excess vitamin C can cause oxalates but normal levels help dissolve oxalates. High meat consumption increases oxalates, excessive salt consumption can cause high oxalates, soda pop contains phosphoric acid which increases oxalates and causes kidney stones. Excess vitamin D intake can cause oxlates most do not recommend get more then 5000 IU of vitamin D and many say 60 IU is enough. High meat consumption can decrease citrate in the body, citrate prevents oxalates. If a person take magnesium citrate it should not be taken often because the body recycles citrate and it can build up in the body causing liver and kidney damage. If a person has metabolic issues that cause acidosis it can lead to oxalates, I post on addressing acidosis. DNA damage from oxidative stress or health issues can cause high uric acid levels which can increase oxalates. Omega 3 oils help reduce oxalates. Celery, carrots, pomegranate, watermelon, pumpkin seed oil. Helps reduce oxalates. Horsetail herb helped me a lot but has an alkaloid that can build up in the body so should not be taken more then three times a week. Citric acid not to be confused with vitamin C reduces oxalates this is why lemon is very good for reducing oxalates. Bear berry and uva ursa contain berberine which reduces oxalates and uric acid. Stinging nettles reduces oxalates and toxins that can cause oxalates. Stay hydrated but avoid water that has been chlorinated or fluorinated it is toxic an increases oxalates.
High Trymethylamines produced from our microbiome breaking down choline and carnetine is converted by Flavon Mono-Oxygenase 3 to Trymethylamine-N-Oxide. TMAO inhibits bile production. Olive oil has been found to prevent our gut microbiome from producing Trymethylamines.
Crushed flax seed and oat haul increases bile flow.
If we do not correct the health issues causing our bile receptors to be inhbited it can lead to Non Alcohol Fatty Liver Disease.
Balancing the immune system
Healing the gut is very important.
information on our gut microbiome.
Things that may help with infections.
Things that can break down scare tissue in the body is autophagy which I have posted on and HSP70 which is another thing I have posted on. Serrapeptase has been shown to break down calcium deposits and aggregates in the body. It must be used with caution. High dosage can start breaking down tissue in the body but low dose will reduce inflammation and help the body heal.
Inflammation and toxins is why so many are ill now days.