One of the most common questions I get when working with patients is “Can my methylation problems cause digestion issues?” This question has come up over and over again as many people with methylation issues also have gut problems at the same time. It wouldn’t be accurate, in a strict scientific sense, to say that methylation issues cause digestion issues. There is no direct 1:1 relationship between the MTHFR gene mutation and digestive issues like GERD, irritable bowel, diarrhea, constipation, bloating, etc. If you look at the scientific literature you simply won’t find a lot of correlation on that specific issue. But scientific literature doesn’t tell us everything!
In fact there is a connection between poor digestion and methylation that involves the health and function of our gallbladder. As you will see the gallbladder plays a major role in optimum digestion and is directly related to methylation and MTHFR genes. Based on the biochemistry involved it is my opinion that the gallbadder is the most methylation-sensitive organ in our body. This might sound like a dramatic statement, but if you follow me through this article you will realize just how much methylation influences the health of our gallbladder.
Gallbladder, Gut and Detoxification
For starters we have to understand what bile is. Bile is basically soap. It performs nearly the exact same functions as your dish soap. Just like dish soap helps cut the grease and fats off your dishes, your bile helps break up the fats in your diet into small pieces. This process is often referred to as the emulsification function of bile – it literally acts like detergent on the fats we eat. Soap also rinses bacteria off your hands and bile rinses bacteria off the lining of your small intestine. This is one big reason why people with bile problems, which come from MTHFR and methylation problems, often develop SIBO.1 Lack of bile means too many bugs stuck to the walls of your upper small intestine, and this is a big issue for people who are struggling to overcome SIBO and get their gut back on track.
Bile is made out of cholesterol, produced in the liver and sent into the gallbladder for storage. By the time bile is in the gallbladder it is a mixture of mainly water, bile salts, fats and half a dozen other minerals and salts.2 This is what is actually supposed to be released after we eat a meal containing fat. Of course “should” doesn’t mean that it always will. High stress lifestyles, low stomach acid, estrogen dominance, toxin and pesticide exposure can all stop the bile from being released. All these things hurt our methylation cycle, which in turn hurts the gallbladder. Gallbladder removal remains one of the most common surgeries performed every year, indicating that a lot of people unknowingly have a methylation problem that is slowly destroying their gallbladder.
In addition to the ingredients listed above, bile does a few other things we might want to know about. The gallbladder doesn’t just help us digest fats, it has a huge influence on detox also. You know that life-critical function that keeps our body clean and healthy? Yeah, the gallbladder is huge for that process. I describe the gallbladder like a fatty trash can, collecting all the garbage that our liver is trying to remove. When that trash can is emptied several times a day it stays pretty clean. But if you are like millions of people who have compromised methylation, then the gallbladder trash can will get pretty sick and inflamed as it stews and soaks in toxic garbage. Yuck!
What ends up in the gallbladder is some pretty toxic stuff. The bile contains xenobiotics (bisphenol A, flame retardants, pesticides, glyphosate, etc.), hormones (thyroid, estrogen, etc.), and heavy metals (mercury, lead, cadmium, etc.).3,4 Obviously if the gallbladder is the garbage can for the liver it will be carrying some nasty compounds. Many of these compounds like estrogen, mercury, and GMO pesticides require methylation to be fully detoxified. People with MTHFR genetics and an imbalanced methylation cycle are going to run out of methyl groups faster than other people. When someone runs out of methylation groups for their body’s biochemistry, the gallbladder will start to malfunction. Here is how that works.
As long as the bile is runny and healthy like dish soap (think about how slippery your soap is!) it will leave the gallbladder and run down into the gut quickly. That will make sure the toxins our liver is trying to remove leave our body in short order during the digestive process. Unfortunately, bile often gets very thick and becomes too sticky. Estrogen is notorious for causing gallbladder problems and women are far more susceptible to gallbladder stones than men. The estrogen women make and the estrogen women take must be removed, via methylation, through the gallbladder. The more estrogen that ends up inside our bodies the more methyl groups and B-vitamins we will need to get rid of it. A whole lot of estrogen (pregnancy, toxins, birth control pills for years, etc.) creates a very high need for methylation. But as you know not everyone can methylate in an optimum way and not everyone has good absorption of B-vitamins from their diet – these people will develop gallbladder problems unless they balance their digestion and methylation.
The vast majority of all our hormones, including estrogen, are removed by the liver. Methylation problems will cause the liver to run out of methyl groups quicker, and force it to use sugar to try to complete the phase 2 detox process – something science calls glucoronidation meaning to glue together with glucose.5 The higher our estrogen levels rise, the more methyl groups and sulfate groups are needed to detoxify the hormone. Eventually the body says “Enough! I have no more methyl groups or sulfate groups to waste on estrogen detox, so we will now use sugar because I have plenty of that.” As you know sugar can be kind of sticky. Bile should not be sticky!
When the liver shifts over to sugar for detoxification, the bile gets thick like molasses. Molasses doesn’t flow very fast, and there is no way bile thick as molasses is going to get out of the gallbladder and into your gut after you eat. Just isn’t happening. The gallbladder at this point just can’t get the bile out fast enough. The sugar being used to detoxify estrogen and other chemicals makes it so sticky that it gets sludgy. Many people find they have gallbladder sludge from an ultrasound, but what they aren’t told is it is caused by the body using sugar in place of methyl groups or sulfate groups. As the sticky, sludgy bile sits day after week after month after year, it begins to inflame and damage the gallbladder. This is when bile gets dehydrated, cholesterol starts to crystalize and the dreaded gallbladder stones begin to form. Not only does this “sticky” situation prevent adequate detoxification of bile, heavy metals, hormones, drugs and other toxins we need to remove, it will eventually create disease in the organ itself.
So the way we prevent this is through optimizing methylation by increasing taurine, phosphatidylcholine, folate, B12, and TMG. Taurine is produced by the methyl cycle, and when taurine is given to rats with gallbladder sludge, their bile gets slippery again and rescues their liver from damage.5 The methylation genes PEMT and BHMT are found in the liver and they make choline phospholipids which are necessary to keep the bile flowing.6 Choline protects the liver and gallbladder against damage from the detergent action of bile and it promotes movement of cholesterol into the bile so it can be removed from the body.7,8,9 When we run out of choline, cholesterol and fat literally get stuck in our liver and muscles, leading to fatty liver disease and muscle damage.10
My protocol for gallbladder support incorporates all of this methylation research with products designed to support all the key pathways mentioned here. Follow the advice you find below and you will be giving your gallbladder the methylation support it needs to take better care of your digestion. If more people took steps to support and protect their gallbladder, we would see a lot less SIBO, fewer surgeries, and a healthier group of people.
Recommended Supplementation for Gallbladder Health:
(This protocol helps whether you still have your gallbladder or even if it has been surgically removed)
Lipo-Gen – 2 tablets with each meal. This formula provides nutrients which help to the liver and gallbladder process fats more effectively and produce increased quantity of bile.†
Blisphora – 1 tablet per day 30 minutes before a meal. This powerful formula combines significant levels of body-ready folate and easy-to-absorb vitamin B12 to support healthy SAMe metabolism , methylation, and neurotransmitter synthesis for a balanced mood.†
Trancor – 2 capsules 3x per day with meals. Helps to support glutathione production in the liver and provides high doses of taurine to improve bile flow; also provides B6 which is necessary for multiple detoxification pathways inside the liver.†
SpectraZyme® Metagest® – HCl stomach acid that will support the digestion and break down of your food. Take this product right at the end of the meal. To find out what dose is best for you, please see the HCl stomach acid instructions page.†
Recommended Supplementation for Healthy Estrogen Detoxification:
Estrofactors – promotes estrogen balance and relieves hormone-related symptoms by increasing methylation and detoxification of estrogen chemicals.†
Meta I-3-C – active ingredient indole-3-carbinol promotes healthy metabolism of estrogen, protects against estrogen-related cancers and optimizes estrogen detoxification.†
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All supplements in this nutritional protocol can be purchased online through Dr. Rostenberg’s online pharmacy. Getting the supplements shipped to your door is very easy. Just follow the instructions below:
These supplements are available from our Metagenics web store and we extend a 20% discount plus free shipping to all new patients who order online. We also give you free shipping and 10% off all recurring orders. You will find our prices are competitive with other outlets.
Just click on “Create an Account” in the top right corner to get started. The practitioner code is RedMountain.
Metagenics batch tests every single raw ingredient. Meaning, they test every batch, every time before it is processed into a supplement. I’m not aware of any other company that puts that kind of expense and effort into product quality.
In closing, methylation problems by themselves won’t give you a digestive issue. What MTHFR and methylation issues will do is weaken the function of your gallbladder. Once that starts, then your digestion can really fall apart. In the modern world of stress, toxins and malnutrition gallbladders are being destroyed at a rapid rate. People just aren’t being educated about the amazing things that bile does for us, nor are they being told how to support optimum gallbladder and bile function. It doesn’t have to be that way for you and your loved ones. Support methylation, keep the bile running, and your gut will thank you!
Yours in Health,
By studying the current peer-reviewed research, Dr. Rostenberg has discovered powerful, natural strategies to optimize gut and methylation function to heal the body. He can help you uncover the genetic or root causes of your health problem and find a natural solution! If you would like help improving your gallbladder and digestion to help reduce/eliminate your symptoms, please contact Dr. Rostenberg at Red Mountain Natural Medicine today. Phone 208-322-7755. Email email@example.com. Website http://www.redmountainclinic.com
- Monte MJ, Marin JJ, Antelo A, et al. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009 Feb 21;15(7):804-16.
- Guyton AC, Hall JE. Textbook of Medical Physiology, 11th ed. Philadelphia, PA: Elsevier, 2006, p. 803.
- Hagenbuch B, Dawson P. The sodium bile salt cotransport family SLC10. Pflugers Arch. 2004 Feb;447(5):566-70.
- Stieger B. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handb Exp Pharmacol. 2011;(201):205-59.
- Sánchez Pozzi EJ, Crocenzi FA, Pellegrino JM, et al. Ursodeoxycholate reduces ethinylestradiol glucuronidation in the rat: role in prevention of estrogen-induced cholestasis. J Pharmacol Exp Ther. 2003 Jul;306(1):279-86.
- Sehayek E, Wang R, Ono JG, et al. Localization of the PE methylation pathway and SR-BI to the canalicular membrane: evidence for apical PC biosynthesis that may promote biliary excretion of phospholipid and cholesterol. J Lipid Res. 2003 Sep;44(9):1605-13. PMID: 12810817
- Smith AJ, de Vree JM, Ottenhoff R, et al. Hepatocyte-specific expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice. Hepatology. 1998 Aug;28(2):530-6.
- Denk GU, Bikker H, Lekanne Dit Deprez RH, et al. ABCB4 deficiency: A family saga of early onset cholelithiasis, sclerosing cholangitis and cirrhosis and a novel mutation in the ABCB4 gene. Hepatol Res. 2010 Sep;40(9):937-41.
- Pasmant E, Goussard P, Baranes L, et al. First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis. Eur J Hum Genet. Mar 2012; 20(3): 277–282.
- da Costa KA, Kozyreva OG, Song J, et al. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006 Jul;20(9):1336-44.
†This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.
†The information provided on this site is intended for your general knowledge only and is not a substitute for professional medical advice or treatment for specific medical conditions. You should not use this information to diagnose or treat a health problem or disease without consulting with a qualified healthcare provider. Please consult your healthcare provider with any questions or concerns you may have regarding your condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
†In the event of a medical emergency, call a doctor or 911 immediately. Reliance on any information provided by this website is solely at your own risk.