Research Related to Enzymes and Intestinal Health
Leaky Gut / Intestinal Permeability
last updated 8.25.05

1. Ambrus JL, Lassman HB, and DeMarchi JJ. Absorption of exogenous and endogenous proteolytic enzymes. Clinical Pharmacol Therapy 1967;8:362–8.

2. Amoss M, et al. Release of gonadotrophins by oral administration of synthetic LRF or a tripeptidle fragment of LRF. Journal of Clinical Endocrinol. Metab. 35: 135-177, 1972.

3. Andre C., et al. Interference of oral immunization with the intestinal absorption of heterologous albumin. Eur. J. Immunol. 4:701-704, 1974.

4. Avakian S. Further studies on the absorption of chymotrypsin. Clin Pharmacol Ther 1964;5:712–5.

5. Bergkvist R. and Svard PC. Studies on the thrombolytic effect of a protease from Aspergillus oryzae. Acta Physiol. Sand. 60:363-371,1964

6. Bjarnason I, et al. Intestinal permeability in celiac sprue, dermatitis herpetiformis, schizophrenia and atopic eczema. Gastroenterology 86: 1029, 1984.

7. Bockman DE, and Winborm WB. Light and electron microscopy of intestinal ferritin absorption: Observations in sensitized and non-sensitized hamsters. Anat. Rec. 155:603- 622,1966.

8. Campbell CA, Forrest J, and Muscgrove C. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1994;343:109–10 [letter].

9. Cichoke AJ. The effect of systemic enzyme therapy on cancer cells and the immune system. Townsend Letter for Doctors and Patients 1995;Nov:30–2 [review].

10. Dannaeus A., et al. Intestinal uptake of ovalbumin in malabsorption and food allergy in relation to serum IgG antibody and orally administrated sodium chromoglycate. Clin. Allergy 9: 263-270,1979.

11. Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: a double-blind study. Pennsylvania Med J 1965;Oct:35–7.

12. DiMagno EP, et al. Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. New England Journal of Medicine 228:813-815, 1973.

13. Ferguson A and Caldwell F. Precipitins to dietary proteins in serum and upper GI secretion of coeliac children. British Medical Journal 1 :75-77,1972.

14. Fitzgerald DE, et al. Relief of chronic arterial obstruction using intravenous brinase. Scandinavian Journal of Thor. Cardiovasc. Surgery 13:327-332,1979.

15. Fitzgerald DE and Frisch EP. Relief of chronic peripheral artery obstruction by intravenous brinase. Irish Med. Ass. 66:3, 1973.

16. Frisch EP and Blomback M. Blood coagulation studies in patients treated with brinase. In: Progress in Chemical Fibrinolysis and Thrombolysis. Vol. IV, J. F. Davidson (Ed.), Edinburgh: Churchill-Livingstone, pp. 184- 187, 1979

17. Frisch EP, et al. Dosage of i. v. brinase in man based on brinase inhibitor capacity and coagulation studies. Angiology, 26:557, 1975.

18. Gardner MLG. Gastrointestinal absorption of intact proteins. Annual Review of Nutrition 8:329-350,1988.

19. Gardner MLG. Intestinal assimilation of intact peptides and proteins from the diet - A neglected field? Biol. Review 59:289-331,1984.

20. Gonzalez NJ and Isaacs LL. Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support. Nutr Cancer 1999;33:117–24.

21. Griffin SM, et al. Acid resistant lipase as replacement therapy in chronic exocrine insufficiency: a study in dogs. Gut, 30:1012-1015, 1989.

22. Gullo L. Indication for pancreatic enzyme treatment in non-pancreatic digestive diseases. Digestion 1993;54(suppl 2):43–7.

23. Hamilton I, et al. Small intestinal permeability in dermatological disease. Q. J. Med., 56:559-567, 1985

24. Heatley RV, et al. Inflammatory bowel disease, In Gut Defenses in Clinical Practice. M. S. Losowsky and R V. Heatley, eds., Churchill Livingstone, Edinburgh, pp. 225-277, 1986.

25. Hemmings WA and Williams EW. Transport of large breakdown products of dietary protein through the gut wall. Gut 19:715-723, 1978.

26. Husby S, et al. Passage of dietary antigens into the blood of children with coeliac disease: Quantification and size distribution of absorbed antigens. Gut, 28:1062-1072,1987.

27. Husby S, et al. Passage of undergrade dietary antigen into the blood of healthy adults: further characterization of the kinetics of uptake and the size distribution of the antigen. Scand. J. Immunology 24:447-455, 1986.

28. Izaka K, Yamada M, Kawano T, and Suyama T. Gastrointestinal absorption and anti-inflammatory effect of bromelain. Jpn J Pharmacol 1972;22:519–34.

29. Jackson PG, et al. Intestinal permeability in patients with eczema and food allergy. Lancet 1:1285-1286, 1981.

30. Jacobson, I., et al Human beta-lactalbumin as a marker of rnacromolecular absorption, Gut, 27: 1029-1034, 1986.

31. Jones R, Franklin K, Spicer R, Berry J. Colonic strictures in children with cystic fibrosis on low-strength pancreatic enzymes. Lancet 1995;346:499–500 [letter].

32. Larson, L. J., et al Properties of the complex between alpha-2-macro-globulin and brinase, a proteinase from Aspergillus oryzae with thrombolytic effect, thrombosis Research, 49:55-68, 1988.

33. Laskowski M., et al, Effect of trypsin inhibitor on passage of insulin across the intestinal barrier, Science, 127: 1115-1116, 1958.

34. Layer P, Groger G. Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency. Digestion 1993;54(suppl 2):10–4.

35. Liebow, C. and Rothman, S. S., Enteropancreatic circulation of digestive enzymes, Science, 189:472-474,1975

36. Loehry, C. A., et al Permeability of the small intestine to substances of different molecular weight, Gut, 11 :446-470, 1970.

37. Lund, F., et al, Thrombolytic treatment with i. v. brinase in advance arterial obliterative disease, Angiology, 26:534, 1975.

38. Kiesslling, H. and Svenson, R, Influence of an enzyme from Aspergillus oryzae, Protease 1, on some components of the fibrinolytic system, Acta Chem. Scand., 24: 569-579, 1970.

39. Kleine MW, Stauder GM, Beese EW. The intestinal absorption of orally administered hydrolytic enzymes and their effects in the treatment of acute herpes zoster as compared with those of oral acyclovir therapy. Phytomedicine 1995;2:7–15.

40. Mackie, R D., et al, Malabsorption of starch in pancreatic sufficiency, Gastroenterology, 80:1220, 1981

41. McCann M. Pancreatic enzyme supplement for treatment of multiple food allergies. Ann Allergy 1993;71:269.

42. McCarthy, C. F., Nutritional defects in patients with malabsorption, Proc. Nutr. Soc., 35:37- 40,1976.

43. Menzies, I. S., Transmucosal passage of inert molecules in health and disease, In Intestinal Absorption and Secretion, E. Skadhauge and K Heintze, eds., MTP Press, Lancaster, pp. 527-543, 1984.

44. Milla CE, Wielinski CL, Warwick WJ. High-strength pancreatic enzymes. Lancet 1994;343:599 [letter].

45. Nakamura T, Tandoh Y, Terada A, et al. Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and short-chain fatty acid excretion in patients with pancreatic insufficiency resulting from chronic pancreatitis. Int J Pancreatol 1998;23:63–70.

46. Oades PJ, Bush A, Ong PS, Brereton RJ. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1994;343:109 [letter].

47. Oelgoetz AW, Oelgoetz PA, Wittenkind J. The treatment of food allergy and indigestion of pancreatic origin with pancreatic enzymes. Am J Dig Dis Nutr 1935;2:422–6.

48. Ormistron B. J., Clinical effects of TRH and TSH after i. v. and oral administration in normal volunteers and patients with thyroid disease, In Thytropin Releasing Hormone (Frontiers of Hormone) Research, Vol. 1), R. Hall, et al, eds., Karger, Basel pp. 45-52, 1972.

49. Patel RS, Johlin FC Jr, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc 1999;50:823–7.

50. Phelan, J. J., et al, Coeliac disease: The abolition of gliadin toxicity by enzymes from Aspergillus niger, Clin. Sci. Molec. Med., 53: 35-43,1977.

51. Powell CJ. Pancreatic enzymes and fibrosing colonopathy. Lancet 1999;354:251 [letter].

52. Roschlau, H. E. and Fisher, A.M., Thrombolytic therapy with local perfusions of CA-7 (fibrinolytic enzyme from Aspergillus oryzae) in the dog, Angiology, 17:670-682, 1966.

53. Seligman B. Bromelain: an anti-inflammatory agent. Angiology 1962;13:508–10.

54. Siefert, J., et al, Mucosal permeation of Macromolecules and particles, See Ref 31, pp. 505-513.

55. Shorter, R G., et al, A working hypothesis for the etiology and pathogenesis of nonspecific inflammatory bowel disease, Am. J. Dig. Dis., 17: 1024-1032, 1972.

56. Stevens JC, Maguiness KM, Hollingsworth J, et al. Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy. J Pediatr Gastroenterol Nutr 1998;26:80–4.

57. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci 1999;44:1317–21.

58. Taylor CJ, Hillel PG, Ghosal S, et al. Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis. Arch Dis Child 1999;80:149–52.

59. Udall, J. N. and Walker, W. A., The physiologic and pathologic basis for the transport of macromolecule's across the intestinal tract, J. Pediatr.. Gastroentarol. Nutr., :295-301,1982.

60. Vanhove, P., et al, Action of brinase on human fibrinogen and plasminogen. Thrombos Haemostas., 42: 571-581, 1979

61. Verhaege, R, et al, Clinical trial of brinase and anticoagulants as a method of treatment for advanced limb ischemia, Eur. J. Clin. Pharmacol., 16: 165- 170, 1979.

62. Verstraefe, M. and Verhaege, R, Clinical study if brinase, a proteolytic enzyme from Aspergillus oryzae, 19th Annual Congr. Intern,. Coll. Angiology, Dublin, Ireland, 1977.

63. Walker, W. A., Antigen absorption from the small intestine and gastrointestinal disease, Pediatr. Clin., North Am., 22:731-746, 1975.

64. Warshaw, A. L., et a, Protein uptake by the intestine: Evidence for absorption of intact macromolecule's, Gastroenterology, 66: 987-992,1974.

65. Wolf, J. L., et al Intestinal M cells: A pathway for entry of retrovirus into the host, Science, 212:471-472, 1981.

66. Wolf M, Ransberger K. Enzyme Therapy. New York: Vantage Press 1972, 135–220 [review].

What Causes Leaky Gut?

Anyone can develop a leaky gut at any time in their lives. Several factors can lead to leaky gut, either occurring individually or working together. Any chemical or physical activity that stimulates the pores in the intestines and keeps them open for too long can lead to increased permeability. Some common sources follow.

Yeast – This is probably one of the primary causes of leaky gut.Yeasts are single-celled organisms that usually reside in the mucosal lining. Yeast can grow out of the single-cell form and into a fungal form. The fungal form grows root-like tentacles (hyphae) that drill deep into the mucosal lining, poking ‘holes’ in the gut.

Excessive environment toxins –With the detoxification system overloaded or dysfunctional, environment toxins from either inside or outside the body may build up. They can irritate the intestinal lining. The constant inflammation and immune system activity can create a more permeable gut wall.

Chronic stress – Stress suppresses the immune system and can alter intestinal physiological function, increase gut permeability, and cause inflammation. A healthy immune system can easily block out typical pathogens, but a weak one may be overrun. When the immune system is overactive for an extended period of time, leaky gut can develop.

Inflammation – Anything causing inflammation may lead to leaky gut. This can result from insufficiently broken-down food or infections of any kind. Maybe the stomach just does not produce enough hydrochloric acid, resulting in improper digestion. Larger particle sizes from any food can irritate the gut lining. Yeast/bacteria/parasites/viruses can all cause inflammation. Besides the physical damage created by an imbalance of microbes in the gut, bacteria and yeast give off many toxins.
see Bacteria
see Yeast
see Viruses

Medications – Medications, prescription and over-the-counter pain relievers such as acetaminophen or ibuprofen, may also lead to increased permeability. They are considered ‘hard’ on the gastrointestinal lining. Aspirin reduces the thickness of the mucosal lining in the gut, thus making it more susceptible to yeast, inflammation, and irritation by food passing through the gut.

Diet – A diet high in sugar, refined flour and processed foods, complete with their rainbow of artificial food colorings, flavorings, and preservatives places a lot of stress on the immune system as well as the liver. Our bodies see most of the artificial chemicals as pure toxins. The more you consume, the more the body must process out. Most processed foods have less nutrition in them as well. So, you use more energy and nutrients processing these foods from your body and receive less energy from the food. A diet high in refined sugar, flours, and artificial chemicals can actually cost you nutrients and energy rather than supply them.
see Feingold Program

Zinc deficiency – Zinc is necessary in maintaining intestinal wall integrity. Supplementing with zinc could contribute significantly to healing a leaky gut in about eight weeks (Sturniolo 2001). Zinc is also instrumental in a maintaining a healthy immune system (Prasad 2002). The synthesis of serotonin involves zinc. Since serotonin is also necessary for melatonin synthesis, a zinc deficiency may result in low levels of both of these compounds, causing problems with the sleep cycle, calming, and hyperness.
see Serotonin

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Problems of Having Leaky Gut

Leaky gut is a condition that can directly lead to many other specific disease states, or indirectly aggravate or worsen other conditions. You may have leaky gut and not be aware of it. Many food intolerances and sensitivities are a consequence of a leaky gut to some degree. You may just feel run down, out of energy, have many food and chemical intolerances, or a multitude of other seemingly unrelated problems. Symptoms of leaky gut syndrome may include:

• aggression • anxiety • asthma • atypical sensory reactions • bed-wetting • bladder infections • bloating or gas • chronic joint, muscle, or abdominal pain • confusion • diarrhea or constipation • fatigue • fevers of unknown origin • fuzzy thinking or ‘brain fog’ • indigestion • memory problems • migraines • mood swings • nervousness • poor exercise tolerance • poor immunity • skin rashes

Besides particles being too large, escaping into the bloodstream, wandering loose in the body, and causing havoc, there is another side to consider. Because the food was not digested and absorbed properly, the person may experience nutrient deficiencies. In one area, the nutrients are bound up in a manner the body does not recognize and hailing in the immune system to remove them. Yet, in another location, the body is starving for those same nutrients. The biological system is overworking unnecessarily in one area while shutting down somewhere else because of insufficient raw materials.

Vitamin therapies may target some of these other systems starving for raw materials. By supplying just the one or two specific raw materials, we may temporarily fix that part, if the vitamin can even reach the intended area of the body, but the system as a whole is still malfunctioning. If the gut is not absorbing food well, then the supplements may not be absorbed well either. A better plan is to fix the hole in the boat (heal the gut).
see Food Sensitivities
see Sensory Integration

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Fixing the Holes in the Boat

Some of the solutions people pursue just address the superficial symptoms. Often better and quicker results will be seen if healing the leaky gut condition is part of the overall treatment program, rather than just focusing on treating the various diseases or symptoms that result from the injured gut. There are several different paths to healing a leaky gut. Some of the primary ones found by research are:

  • digestive enzymes
  • probiotics
  • zinc
  • oats/oatmeal (see study below)

There are other supplements such as essential fatty acids or aloe vera which help some people.

Digestive enzymes may be extremely helpful with leaky gut situations because they tackle the problem on several fronts. Enzymes break down the food particles so they do not exist as larger particles that will physically irritate the gut lining or activate the immune system. Plant or microbe (fungal)-based enzymes are especially effective because they do much of this breakdown in the stomach before the food even enters the intestines, a good 60 to 90 minutes before pancreatic enzymes emerge on the scene. Then, by breaking the food down, enzymes are also freeing the individual vitamins, minerals, and other nutrients so the body can use them as the raw materials it needs as well as releasing the energy from your food. Normal biological processes can proceed. Because your nutrition comes from food, you then do not have to supplement extra vitamins, minerals, and whatever else to make up for what you eliminated through diet. Nutrition from whole foods is generally more effective than from many supplements too.

Because enzymes can process the food particles down to their essential forms, anything that does leak through the gut while it is healing is less likely to provoke a negative reaction. Enzymes work on the foods you do suspect as well as those you don’t, or unknown sources. Food intolerances usually drop off dramatically when enzyme use begins. Many people report improvements the very first day of taking enzymes. However, because some food intolerances are processed out of the body a few days later, it is very common to hear of significant improvement by the end of the first week on enzymes.

Next, enzymes proactively support intestinal health. They can act as trash collectors removing dead tissue, debris, chemicals, and toxins from the body. This cleaning out allows the gut to heal faster. Another bonus is that enzymes are effective at clearing out pathogens that may cause and contribute to damaging the gastrointestinal tract. Bacteria and parasites are made of proteins, viruses have protein coatings or ‘films,’ and yeasts have outer shells consisting of cellulose and protein. Proteases and cellulases can help break these intruders down, and then carry off the toxins and dead cells the destroyed pathogens leave behind.

If the digestive enzymes themselves are absorbed into the bloodstream along with the other things, this can be very beneficial. Enzymes, especially the proteases that break down proteins, travel through the bloodstream cleaning out any gunk, toxins, and waste that may be accumulating there. They selectively latch onto toxins and escort them out of the body leaving the good tissue and red blood cells to carry on. This assistance in cleaning the blood helps relieve the burden on the liver and the immune system. Enzymes help clear out the traffic jams so everything can get back on schedule. Proteases are often given in between meals for just this purpose. If you give proteases with food, the enzymes will act on the food first, so giving them between meals sends them directly into the bloodstream to do cleanup. Substantial scientific research has established that the bloodstream takes up enzymes intact where they work in this way (Leibow and Rothman 1975; Rothman, Liebow, and Isenman (2002).

Another benefit of taking proteases between meals is to reduce inflammation. Bromelain and papain (protease enzymes derived from pineapple and papaya) have undergone study in great detail for this purpose and are found to be incredibly effective at reducing inflammation. Proteases can reduce inflammation in the gut directly. Bromelain and papain are well-known agents for assisting in healing gastric ulcers. Material leaking through the intestinal lining can make its way to joints and aggravate them to the point of inflammation, or add to inflammation already started. The proteases in the bloodstream break down these sources of inflammation as they pass by in the bloodstream. Then the debris is transported out of the body, freeing the immune system up to do other things, and allowing you to enjoy your life without so much pain.

The nice thing about enzymes is they address the damaged gut, problematic peptides, food intolerances, and nutrient deficiencies all at the same time. You cover a lot of territory by taking just this one type of supplement.

A good probiotic will help restore the needed balance among the bacteria, yeast, and other microorganisms. Out with the bad and in with the good. A consistent supply of probiotics is like tending a lawn. You need to kill the weeds, and then keep seeding with the ‘good’ grasses. A healthy lawn will need just a little maintenance. However, doing no maintenance will very soon give you a yard overrun with weeds again.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Is Malabsorption the Same as Leaky Gut?

Although you can have both conditions, and they are related, they are technically different. Leaky gut can be caused by a variety of things and can very often lead to malabsorption. Leaky gut is the state
where the protective gut lining looses its integrity. It is less capable of properly selectively screening out those elements that should be screened out, and allowing those elements in that should be let in. So items that should be screened out gain access in.

Malabsorption means 'bad absorption of some type for some reason'. It doesn't indicate the cause though. Nutrients are not being absorbed properly. You might have leaky gut involved, but you can also have malabsorption without leaky gut. If you have a pancreatic problems, poor stomach acid, various diseases, or other causes, you might have an intact gut lining but for some reason, some nutrients are not being absorbed properly. This might be many nutrients or only a few in particular.

What is nice about digestive enzymes is they can help both a leaky gut and malabsorption at the same time.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Research
Enzymes and Leaky gut/intestinal problems

Oats Healing the Gut

J Pharmacol Exp Ther. 2001 Nov;299(2):442-8.
Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. PMID: 11602653

Keshavarzian A, Choudhary S, Holmes EW, Yong S, Banan A, Jakate S, Fields JZ.

Only 30% of alcoholics develop liver disease (ALD) suggesting that additional factors are needed. Endotoxin is one such factor, but its etiology is unclear. Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes. We conclude that chronic gavage of alcohol in rats is a simple experimental model that mimics key aspects of ALD, including endotoxemia and liver injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxemia and ameliorated liver damage in rat, our results suggest that alcohol-induced gut leakiness 1) may cause alcohol-induced endotoxemia and liver injury and 2) may be the critical cofactor in the 30% of alcoholics who develop ALD. Further studies are needed to determine whether ALD in humans can be prevented by preventing alcohol-induced gut leakiness, studies that should lead to the development of useful therapeutic agents for the prevention of ALD.

 

 

Selecting Products
Which Enzymes?
Dosing Guidelines
Mixing Suggestions
Interactions w/ other things
What to Expect Starting
General Trends
At School
Getting Started Step-by-Step
Enzyme Safety

Sensory Integration
Migraines/Pain
Digestive Disorders
Food Sensitivities

Leaky Gut
Bacteria / Yeast
Viruses

PDD/Autism Spectrum
AD(H)D

Autoimmune / Neuro Cond.
Cancer
Celiac
Heart/ Vascular Health
Sports Medicine

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