Saturday, June 30, 2007

Enzymes and Digestion

Digestion and Enzymes
Captured from: Enzyme Stuff

last updated 8.25.05


How digestion works
Here is a very nice illustration and simple description of the digestive tract:
Illustration of Gastrointestinal Tract


Where Enzymes Work in the Gut
This is an important consideration when considering enzymes. First, amylase is contained in everyone's saliva. Amylase is the enzyme that breaks down carbohydrates. When you chew carbs/breads, it becomes sweeter as you chew because the mechanical action of your teeth and amylase in the saliva are breaking the carbohydrates down to their component sugars.

Next, the foods goes to the stomach where it resides about 60 minutes or more as it is further digested by the stomach acid and pepsin. Pepsin is a protease enzymes released into the stomach. There is more mechanical breakdown too by the stomach muscles. If you take plant enzymes, most plant enzymes are quite stable in the stomach environment and go to work. This gives the plant enzymes an edge on digestion over animal/pancreatic enzymes. Plant enzymes can be working on food for at least an hour before the food proceeds to the small intestine.

Once the food enters the small intestine, plant enzymes continue to work. At this point, any pancreatic or animal enzymes kick in. It is at this point that your naturally produced pancreatic enzymes are released by the pancreas. Some enzymes are released by the small intestine lining as well.

The enzymes from the small intestine include:

1. lactase (breaks down milk sugar),
2. DPP IV (breaks down milk protein and other protein bonds), and
3. dissacharrides (breaks down some starches and sugars).

Anything that disrupts the small intestine may also disrupt the production and release of these enzymes. If you have a leaky gut, inflammation, yeast, or something else which hampers the small intestine, then you are likely to also have trouble digesting the foods these enzymes work on.

So any time the gut lining gets injured, these enzymes may not be available for digesting food. An injured gut can also become 'leaky'. Thus the food not digested can become a problem. So it is rather the gut is injured and digestion in interrupted, and not that the food is the problem to begin with.

One strategy is to take out all offending foods (i.e a gluten-free/casein-free diet or GFCF), however, the gut will still be injured in this case and ANYTHING you eat can become a problem because the 'new' foods substituted in may also be insufficiently digested as well. This is why people who think they are starting a GFCF diet end up slowly taking out 28 other main foods as well. The strategy of the Specific Carbohydrate Diet is that all foods requiring these enzymes are eliminated until the gut heals. Then you can return to eating those foods again.

Another strategy is to take measures to proactively heal the gut. A direct way to heal the gut is with digestive enzymes, but there are also other supplements that help too. Enzymes help heal the gut for a number of reasons that have been proved clinically.

Once the gut lining heals, the cells in the lining 're-grow' and your natural digestive enzymes start producing again. Thus the once problematic foods are now not a problem.

Note: a true allergy work via a different mechanism altogether as I understand it, so this would not apply to true allergies. This is food sensitivities/intolerance issues.

Where Nutrients are Absorbed in the Gut

This link (below) describes which nutrients are absorbed in which part of the intestines. If the gut is injured in one particular section, you may have a malabsorption or deficiency of the nutrients which should be absorbed there. However, it may not be possible to determine one and only one region.

Nutrient uptake and other information



Animal versus Plant Enzymes

Plant enzymes are much more stable over a wider pH and temperature range. The stomach is very acidic whereas the small intestine is more alkaline. This is why plant enzymes can work effectively in the stomach, whereas animal-derived or pancreatic enzymes cannot. Most pancreatic enzymes need to be enterically coated to survive the stomach environment.

Plant enzymes can be customized more because they are derived from plant or microbe sources. Pancreatic enzymes are limited to a ratio of proteases (proteins), amylases (carbohydrates), and lipases (fats).

Food is not absorbed in the stomach. The big advantage of plant derived enzymes is that they can be pre-digesting food in the stomach for 60 minutes or much longer before the digested food even gets to the small intestine where it can be absorbed. By the time the digesta hits the small intestines which may be damaged, it is far less likely to provoke a negative reaction even if it crosses into the bloodstream. And it is far more likely to be absorbed and used as nutrition.

With pancreatic enzymes, the food can be absorbed in a poorly digested state before the pancreatic enzymes even get out of their enteric coating and start working.



The Pancreas and How It Works
This section written by Dr Devin Houston and used here with permission

What is the pancreas?

The pancreas is an organ which serves to main purposes: production of hormones that regulate blood glucose levels, and to produce and secrete digestive enzymes and sodium bicarbonate.

What causes the pancreas to make enzymes?

There are 3 roles the pancreas serves in regard to digestive enzymes. First, it produces enzymes, in an inactive form, within the cells of the organ. Second, it stores these inactive enzymes, and third, the pancreas secretes the inactive enzymes into the duodenal portion of the small intestine at an appropriate time.

How does the pancreas function in digestion?

The pancreas is located under the stomach and liver, within a fold of the small intesine and functions by reducing the acidity of stomach contents as it enters the duodenum, the first part of the small intestine. It does this by shooting out a mixture of proteins and sodium bicarbonate. This mixture, containing inactive enzymes and bicarbonate, is stored in a duct from the pancreas leading into the duodenum. Pancreatic enzymes are continuously produced by the pancreas, and stored until food is sensed in the small intestine.

What triggers the pancreas to push enzymes into the duodenum?
A number of factors are involved in pancreatic secretion, and is thought to be divided into 3 phases: cephalic (brain), gastric (stomach), and intestinal. The cephalic phase contributes appx. 25% to the pancreatic response, and is controlled by the vagus nerve. The stimulants are sight, smell, taste and eating of food. The gastric phase contributes 10% to the response, and is also via vagal innervation, mainly through stomach distention as it fills with food. The remainder, some 50 – 75% is due to the intestinal phase, mediated by GI hormones (such as secretin and cholecytokinin, aka CCK), and stimulated by amino acids, fatty acids, calcium, and stomach acid. In addition, the pancreas produces a specific peptide known as pancreatic polypeptide (PP), which acts to negatively feedback on pancreatic secretion; that is, it inhibits enzyme secretion. PP is released in response to vagal nerve stimulation.

What is the sequence of biochemical events that regulate pancreatic enzyme secretion?
The pancreas actually is always secreting pancreatic fluid into the duodenum, even between meals. This amount is about 0.2 – 0.3 ml per minute and increases greater than 3 mls per minute in response to a meal. Pancreatic secretion contains proteins in a concentration of about 7 mg/ml during stimulation by secretin and CCK, most of this protein is enzymes. All of the enzymes are secreted as inactive precursors, which are activated by previously activated stomach enzymes.

The most important stimulus for pancreatic stimulation is a meal. The factors controlling the pancreatic response include both chemical composition and physical properties of the meal. The strongest stimulants to pancreatic enzyme secretion are fatty acids and monoglycerides. By themselves they can stimulate maximal enzyme output. Proteins are next, while carbohydrates have little stimulatory action. These nutrients exert their action in the duodenum. The most important factor appears to be the area of contact of nutrient with the mucosa. Therefore, it is the load of nutrient in the case of fat or protein delivered to the duodenum, rather than the concentration, which determines the magnitude of stimulation. Homogenized meals stimulate pancreatic secretion for shorter periods of time, since they leave the stomach more rapidly.

As the acidic chyme, or food mass, enters the duodenum, the acid stimulate the enteroendocrine S cells (specialized endocrine cells in the duodenum) to release a gastrointestinal hormone called secretin, which then stimulates the pancreatic cells to secrete the enzymes and bicarbonate. The presence of partially hydrolysed fat (fatty acids) and protein (amino acids and peptides) in the chyme that enters the duodenum, as well as the acidic pH of the chyme, stimulates enteroendocrine I cells in the upper small intestine to release the hormone cholecystokinin (CCK), which also causes secretion of enzymes and bicarbonate. These same hormones also stimulate bile secretion into the duodenum. Although the digestion of most nutrients in the small intestine is extensively carried out by enzymes secreted by the pancreas, enzymes located at the brush border membrane of the enterocytes are responsible for the completion of this process.

How then is the pancreas regulated?
From the above explanation, there are obviously three areas of potential regulation: cephalic, gastric, and intestinal.

Cephalic regulation is under the control of the parasympathetic nervous system. This system controls salivation which occurs in response to smelling, seeing, and tasting food. The GI tract is connected to the same part of the nervous system, so this stimulation will effect pancreatic secretion. The only way to inhibit pancreatic secretion via this mechanism is to disturb the vagal innervation of the pancreas, which is not easily done in humans.

Gastric regulation plays a minor role, but stomach distention due to food stimulates a vagal response, which in turn stimulates pancreatic secretion. This is not subject to an inhibitory feedback mechanism.

The intestinal response is mainly under the control of GI hormones, namely secretin and CCK. Secretin production occurs when the acidic chyme enters the duodenum. CCK is released in response to the “pre-digestion” that occurs in the stomach from pepsin and lipase enzymes. The resulting amino acids and fatty acids from these enzymes stimulates CCK release, which then stimulates pancreatic secretion and bile production. Obviously, these hormones represent a point of regulation for pancreatic secretion, that is, decreasing the production of secretin and CCK hormones should also decrease pancreatic enzyme secretion. There is data to suggest that bile acids can cause an inhibition of CCK release, which would then effect pancreatic enzyme production.

Does diet effect pancreatic enzyme secretion?
Yes. It has been shown that certain foods have high amounts of enzyme inhibitor, notably soybeans and other legumes. When on a diet of high soy, animals would develop larger pancreases, and their enzyme secretion would increase. Specific inhibitors of pancreatic enzymes, when given to humans, can cause an increase in that specific enzyme by the pancreas. This infers that some type of feedback mechanism exists for pancreatic enzyme secretion. It is also known that the products of proteolysis and lipolysis (amino acids and fatty acids) stimulate the hormones that cause pancreatic secretion to occur. If starch and glucose is placed in the small intestine, one sees less protease produced, but more carbohydrase produced. It is also apparent that adaptation plays a big role in pancreatic secretion. Prolonged intake of certain foods seems to stimulate production of pancreatic enzymes specific for the digestion of that food. Some peptides derived from milk casein seem to also stimulate enzyme production in rats, as does GABA.

Does taking oral enzymes have an inhibitory feedback on pancreatic enzyme secretion?
This has been an area of controversy for some time. Some of this confusion is due to the fact that animal studies don’t often predict what happens in humans. The digestive process is different in rodents than in man, so many of the early studies in animals aren’t applicable to humans. In rodents, enzyme secretion is increased if you quickly remove the pancreatic juice from the intestine. Such a mechanism has not been demonstrated in man.

A Swiss study in 1998 (Friess H. Int. J. Pancreatology 23:115) demonstrated no changes in human pancreatic enzyme secretion after 4 wks of oral pancreatic enzyme therapy at conventional doses. In 1997, a German study (Dominguez-Munoz JE, Aliment Pharmacol. 11:403) indicated a small decrease in pancreatic elastase in human males with a preparation of enteric-coated pancreatic enzyme microtablets, but not with enteric-coated enzyme tablets, indicating that the enzyme preparation or excipients present may have an effect on the study results. The same study showed that the pancreatic effect was not due to inhibition of GI hormones. Another earlier study (Mossner J, Pancreas 6:637, 1991) showed that an extract of pig pancreas placed in the lower small intestine actually increased pancreatic enzyme production, but if pure trypsin protease was used (a pancreatic enzyme) instead, a decrease in pancreatic secretion was observed, but only at very high trypsin levels. Most recently, Walkowiak et al. (Eur J Clin Invest. 33:65, 2003) showed that pancreatic enzymes at very high levels (5 grams per day for 7 days) could decrease pancreatic elastase measured in feces by as much as 50%. This effect was reversed when enzymes were discontinued. Smaller doses of enzyme did not show a significant effect on pancreatic secretion. There is a question as to whether the assays used in that particular study were appropriate for the experimental design, as the oral enzymes interfered with the fecal enzyme testing. Controls for the enteric coatings of the enzymes were not addressed.

Should parents be concerned about giving plant based enzymes to children?
No. There is no evidence that PLANT-based enzymes have any effect on pancreatic enzyme secretion. All the studies mentioned previously used PANCREATIC oral enzymes, which have the same enzyme proteins as human pancreas. Such similarities between oral enzymes used and pancreatic enzymes may explain some of the study results. Plant enzymes, while performing similar functions as pancreatic enzymes, are different in structure from pancreatic enzymes. Pancreatic enzymes are different from plant enzymes. Plant enzymes do the majority of their work in the intestinal tract, and are not enteric coated. Even if plant enzymes did inhibit pancreatic secretion through feedback inhibition, the effect would not be permanent, and would be remedied simply by stopping the enzyme.

If supplementing the diet with oral enzymes was deleterious to health, then eating raw foods, such as fruits and vegetables, might also pose a hazard, as those foods are high in enzymes. Since no hazard has been noted from eating such a diet, we can conclude that plant enzymes represent no source of harm.

Conclusions
Pancreatic enzyme secretion is regulated in a complex manner by several pathways, not all subject to feed back inhibition. All studies regarding the effects of oral enzyme supplementation on pancreatic function have been performed with pig pancreatic enzyme preparations. Whether any oral enzyme has an influence on pancreatic enzyme secretion is still not clear, as studies to date have been few and inconclusive, which may be due to experimental artifacts and methods used. Plant-based enzymes have not been studied to the extent of pancreatic enzymes. However, active digestive-like enzymes are very prevalent in raw foods and are considered a healthful part of diet. Plant enzymes have obvious advantages over pancreatic enzymes as oral supplements, due to their increased stability and lack of need for enteric coating, and difference in physical structure from pancreatic enzymes. In summary, one need not be concerned about supplementing children’s diet with plant-based enzymes, as the doses used for normal digestive support are quite small in contrast to the oral pancreatic enzymes used for those studies to elicit a positive result.

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Additional Notes

So if supplementing enzymes has never been reported to have caused the pancreas to permanently stop producing enzymes, where did this idea even come from? Some people may be assuming pancreas function is similar to thyroid function and 'if you don't use it you will lose it.' Supplementing the thyroid may result in it stopping to make thyroid hormone. Normal thyroid function may not revive when the supplement stops. This may be true of that endocrine issue, but pancreatic enzymes are different. They are EXOcrine and operate differently.


Stomach Acid
More on this section coming...but start with this:

Here is an animation showing the stomach acid production process:
Acid Secretion

And here is an article with illustrations on how food intolerances can lead to the promotion of extra histamine and other chemicals being released, and possibly causing cell disruption, due to the immune system response:
Article: Food Intollerances.

Here is an animation showing how the proton pump acid inhibitors work:
How the PPI works.


Enzymes That Work on Specific Food Types or Compounds
Specific enzymes work on specific foods. You need the right type of enzyme for the foods you want it to break down. Think of the foods you have problems with and then choose a product that contains at least those types of enzymes. Here is a list of the common enzyme types and foods they act on.

Digestive enzymes are enzymes that break down food into usable material. The major different types of digestive enzymes are:

• amylase – breaks down carbohydrates, starches, and sugars which are prevalent in potatoes, fruits, vegetables, and many snack foods

• lactase – breaks down lactose (milk sugars)
• diastase – digests vegetable starch
• sucrase – digests complex sugars and starches
• maltase – digests disaccharides to monosaccharides (malt sugars)
• invertase – breaks down sucrose (table sugar)
• glucoamylase – breaks down starch to glucose
• alpha-glactosidase – facilitates digestion of beans, legumes, seeds, roots, soy products, and underground stems

• protease – breaks down proteins found in meats, nuts, eggs, and cheese

• pepsin – breaks down proteins into peptides
• peptidase – breaks down small peptide proteins to amino acids
• trypsin – derived from animal pancreas, breaks down proteins
• alpha – chymotrypsin, an animal-derived enzyme, breaks down proteins
• bromelain – derived from pineapple, breaks down a broad spectrum of proteins, has anti-inflammatory properties, effective over very wide pH range
• papain – derived from raw papaya, broad range of substrates and pH, works well breaking down small and large proteins
• lipase – breaks down fats found in most dairy products, nuts, oils, and meat

• cellulase – breaks down cellulose, plant fiber; not found in humans

• other stuff
• betaine HCL – increases the hydrochloric acid content of the upper digestive
system; activates the protein digesting enzyme pepsin in the stomach (does not
influence plant- or fungal-derived enzymes)
• CereCalase™ – a unique
cellulase complex from National Enzyme Company that maximizes fiber and cereal
digestion and absorption of essential minerals; an exclusive blend of synergistic phytase, hemicellulase, and beta-glucanase
• endoprotease – cleaves peptide bonds from the interior of peptide chains
• exoprotease – cleaves off amino acids from the ends of peptide chains
• extract of ox bile – an animal-derived enzyme, stimulates the intestine to move
• fructooligosaccharides (FOS) – helps support the growth of friendly intestinal microbes, also inhibits the growth of harmful species
• L-glutamic acid – activates the protein digesting enzyme pepsin in the stomach
• lysozyme – an animal-derived enzyme, and a component of every lung cell; lysozyme is very important in the control of infections, attacks invading bacterial and viruses
• papayotin – from papaya
• pancreatin – an animal-derived enzyme, breaks down protein and fats
• pancrelipase – an animal-derived enzyme, breaks down protein, fats, and carbohydrates
• pectinase – breaks down the pectin in fruit
• phytase – digests phytic acid, allows minerals such as calcium, zinc, copper, manganese, etc. to be more available by the body, but does not break down any food proteins
• xylanase – breaks down xylan sugars, works well with grains such as corn
Other general terms for enzymes referring to their general action instead of specific action
  • Endopeptidase: Enzymes that cleave proteins only on the inside
  • Exopeptidase: Enzymes that cleave proteins only on the outside (terminal) part
    • Aminopeptidase: Exopeptidase that cleaves at the amino terminating end
    • Carboxypeptidase: Exopeptidase that cleaves at the carboxy terminating end



Digestion and Enzymes
Dairy Increasing Villi

O Ruminants
O Non-ruminants




Animal Research

O Cats
O Dogs
O Reptiles
This independent site is for education and information about digestive enzymes. There is a large need to provide practical and general information on enzyme therapy for a wide range of uses.

Enzymes have been around a very long time. Hopefully this site will help reduce the learning curve.

Ideas, comments, and questions are welcome.

Site Information for Enzyme Stuff


To view information on another Digestive Dosease, Click on Digestive Diseases Library!
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Digestive Diseases Library

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