Stomach acid, bile and enzymes

The groundwork in the stomach and small intestine determines what reaches the large intestine.

How solid is the research? Well supported

The physiology of digestion is very well understood. Diagnosis and treatment of pancreatic insufficiency are set out in guidelines. Many “natural” digestive aids, however, have barely been studied.

Cause or consequence? Cause and consequence

Weak digestion comes from overgrowth, from lack of bile — and from a link missing in the digestive chain. It explains bloating and nutrient deficiency and favours overgrowth further.

Healthy state

Digestion means breaking down, absorbing and moving on, and it starts before the first bite. Seeing, smelling and expecting food set saliva and gastric juice in motion via the Vagus nerve The tenth cranial nerve and the most important nerve of the rest-and-digest system. It connects the brainstem and the abdominal organs; most of its fibres tell the brain what is happening in the gut. More in the chapter “The vagus nerve: the data line between belly and head” (the nerve that runs the abdomen at rest). Chewing then breaks the food up and enlarges the surface that enzymes can attack. The salivary glands make roughly one to one and a half litres of saliva a day. It lubricates the bite and contains amylase, which starts on the starch.

The stomach is mixer, acid bath and portion control in one. Its parietal cells make hydrochloric acid, and on an empty stomach the pH is around 1 to 2. The acid activates pepsin, which starts cutting protein, releases minerals such as iron and vitamin B12 from food, and kills a large share of the germs you swallow. That is a real protective barrier. The same cells make intrinsic factor, a protein that later allows vitamin B12 to be absorbed in the last section of the small intestine. The stomach passes the pulp to the duodenum in small portions: liquids go quickly, fatty solid foods stay considerably longer. Depending on its makeup, a meal usually stays two to four hours.

Most of the work happens in the small intestine. The pancreas and bile supply enzymes and Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea”, and the lining absorbs the building blocks. Folds, villi and the brush border (tiny projections of the cells) enlarge its surface to many square metres. Each section has its own job: iron is absorbed at the top in the duodenum, fats and many vitamins in the middle, vitamin B12 and bile acids only at the very end, in the Ileum The last section of the small intestine. It recovers bile acids, absorbs vitamin B12 and joins the colon via the ileocaecal valve. More in the chapter “Where the small intestine meets the colon: ileum, valve and caecum”. That is why problems at different sites show up as different deficiencies. How the signals between stomach, bile and pancreas run is covered in the chapter on the digestive chain, who supplies which enzyme in the chapter on digestive enzymes.

Between meals the gut switches to cleaning. When fasting, about every 90 to 120 minutes a strong wave of muscle contraction runs from the stomach to the end of the small intestine, the MMC ( Migrating motor complex A wave of muscle contractions that sweeps the stomach and small intestine empty about every one and a half to two hours when fasting. Eating interrupts it. More in the chapter “Intermittent fasting and meal timing: 16:8, 5:2 and Ramadan”, the “housekeeping wave”). It sweeps leftovers and bacteria towards the large intestine and keeps the small intestine thinly populated. Every meal interrupts it, and afterwards it needs several hours without food to start again. Constant snacking leaves it little room.

What has not been absorbed by now reaches the large intestine through the ileocaecal valve, the sphincter between small and large intestine. There bacteria turn fibre into Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids”, and the lining draws water out of the pulp. Each stage hands the next material in a certain form, and the stages have reserves: the pancreas, for instance, has to fail to a large degree before fat is really poorly digested. This explains why digestive problems often grow unnoticed for a long time and then seem to appear suddenly.

Stomach acid, bile and enzymes break food down, the small intestine absorbs it.

Disrupted state: causes and effects

Less stomach acid results from acid blockers ( Proton pump inhibitors (PPIs) Acid blockers such as omeprazole or pantoprazole. They inhibit the acid pump in the stomach lining. More in the chapter “Acid blockers (PPIs): what they change in the gut and how to stop them properly”), but also from chronic inflammation of the stomach lining (atrophic gastritis, for example after a long Helicobacter infection or through an autoimmune reaction) or after stomach surgery. Without acid, the protective barrier is missing: more germs from the mouth and food reach the gut, some gastrointestinal infections become more likely, and in long-term users of acid blockers studies find lower Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity” diversity, with more mouth bacteria in the stool. That does not mean every use does harm. For reflux disease, stomach ulcers or stomach protection, these drugs are important and effective.

Less acid and a lack of intrinsic factor make it harder to absorb vitamin B12, and iron and some minerals dissolve less well. This develops slowly over years. Tiredness, tingling in the feet or anaemia often show up late. Not every long-term user develops a deficiency. The risk rises with additional factors such as older age, a strict vegan diet or the diabetes drug metformin. More in the chapter on nutrient deficiencies.

If the pancreas works too little (exocrine pancreatic insufficiency), fat remains undigested. Causes include chronic inflammation (alcohol, smoking), surgery, diabetes or Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances”. Typical signs are greasy, pale, foul-smelling stools that float or are hard to flush away, plus bloating, weight loss and later a lack of fat-soluble vitamins. A single greasy stool after a very fatty meal, by contrast, means nothing. If bile acids are not fully reabsorbed in the last section of the small intestine, they irritate the large intestine and cause watery diarrhoea; see the chapter on bile acids.

Not only chemistry but also movement counts. If the stomach is sluggish, for example in diabetes, after an infection or without a visible cause ( Gastroparesis Delayed gastric emptying without a mechanical obstruction, with nausea, vomiting, early satiety and fullness. More in the chapter “Gastroparesis: when the stomach empties too slowly”), food stays too long and causes fullness, nausea and belching. If the MMC housekeeping wave is weak, for example after a gastrointestinal infection or under drugs such as opioids, bacteria can settle more easily in the small intestine ( Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised”). Hasty eating on the side and lasting stress can also dampen the preparation via the vagus nerve. For the effect on symptoms there are so far mostly physiological explanations and few direct studies.

Many complaints are easily mixed up. As a rough rule of thumb, not a diagnosis: fullness during or shortly after eating points more to the stomach, a bloated belly one to three hours later more to the small intestine or a sugar intolerance (the undigested sugar only ferments in the large intestine, but often arrives there within one to two hours), complaints only the next day more to the large intestine. Heartburn does not automatically mean too much acid. Undigested bits such as corn kernels or skins in the stool are normal, because humans cannot split cellulose. What you can observe yourself: when symptoms appear after eating, how fatty the meal was, stool shape and whether it floats, and weight trend. That helps a medical work-up more than any self-diagnosis.

Little acid, bile or enzymes: undigested food moves on and is fermented by bacteria.

Where it comes from and where it leads

The same symptoms can have different roots. This map shows what may be involved in this problem and what may follow from it.

Connections, not certainty: a link means “can”, not “must”. What applies to you is best clarified in a talk with your doctor.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Chew thoroughly Chewing breaks down food, gives salivary amylase time and starts digestion in the mouth. This has hardly been studied directly for symptoms, but it is physiologically well founded and costs nothing. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1]
Smaller portions Smaller meals ease the load on the stomach and pancreas and reduce the feeling of fullness. Large, very fatty meals stay in the stomach for a long time. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Cut down on alcohol and smoking Both are a main cause of chronic inflammation of the pancreas and thus of lasting enzyme deficiency. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2]
Eat calmly and leave gaps Sit down to eat and eat without distraction so that the preparation via the vagus nerve can run. Between meals, three to four hours without food help, because the MMC housekeeping wave only runs when fasting. This is worth a try especially with bloating or a tendency to small intestinal bacterial overgrowth. It is physiologically plausible but has hardly been studied as a treatment. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [3][4]
Note symptoms with timing For a few weeks, write down what happens when after eating, what the stool looks like and how your weight develops. This lets you spot patterns, such as stomach symptoms straight away or bloating later, and raise them in a targeted way. The site’s symptom diary is made for this. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

Bitters Bitters are traditionally used to stimulate gastric juice and bile. Good human studies are lacking. Experimental How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Over-the-counter digestive enzymes They do not replace a medical check-up. In real pancreatic insufficiency, prescribed enzymes at a sufficient dose are needed. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Get greasy stools checked Faecal elastase is the usual test for pancreatic insufficiency. If it is confirmed, enzymes taken with meals are effective and recommended in guidelines. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2]
Review acid blockers regularly Discuss with your doctor whether the dose can be lowered or the drug stopped. Usually it is reduced step by step; the US specialist society also considers stopping at once possible. Either way, acid can rebound for a few weeks; this is usually not a relapse. More in the chapter on acid blockers. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5]
Have vitamin B12 checked if at risk If you take acid blockers or metformin long term, eat strictly vegan, are older or notice signs such as tiredness and tingling, the vitamin B12 status can be measured in the blood. This is simple, and a deficiency is easy to correct. Routine testing for every acid blocker user is not recommended. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [6][7]
Clarify the stomach lining and Helicobacter If upper abdominal complaints such as pressure, early fullness or burning persist, a test for Helicobacter pylori (breath or stool test) is usual. An infection can be treated with a combination of drugs. With alarm signs such as weight loss, trouble swallowing, vomiting blood or black stools, an endoscopy should follow quickly. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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