Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Saturday, July 4, 2009

An Autoantigen for Pancreatitis

Pancreatic Secretory Trypsin Inhibitor (PSTI) Has Internalization Basic Triplet

Pancreatitis is an inflammation of the pancreas resulting from lack of adequate inhibition of proteases. Autoantibodies against PSTI would explain some forms of pancreatitis.

I was researching the maintenance of baby gut flora by mother’s milk, when the reference discussed here was brought to my attention by my wife, who happens to be a lactation consultant. The paper showed that PSTI is present in colostrom, the first milk that a baby gets, before the true milk comes in. PSTI protects the new gut from digestion by its own pancreatic proteases, since PSTI is a protease inhibitor that sticks to the gut.

I naturally assumed that PSTI stuck to the gut by heparin-binding domains that would stick to the heparan sulfate proteoglycans on the gut surface. [Recall that it is via these HSPGs that viruses and bacteria infect the gut and the HSPGs in turn are protected during infections by the release of heparin from mast cells. The heparin in the guts of cattle and pigs are used to make commercial heparin to block blood clotting.] So I looked up the structure (above, with basic amino acids in blue and basic triplet on right) sequence of human PSTI at NCBI:

>gi|190694|gb|AAA36522.1| PSTI

The basic triplet (RKR,arg-lys-arg), from my perspective, should result in presentation to the immune system during high levels of inflammation, and as a consequence result in autoantibodies against PSTI. The result would be the neutralization of the protease inhibitor and damaging production of active protease to attack the pancreas, i.e. pancreatitis.

It would be fairly easy to test this hypothesis by looking for the anti-PSTI antibodies in some people with pancreatitis. Other autoantibodies, e.g. against tissue transglutaminase, might also be checked, because the inflammation that produced one autoantibody may produce others and both PSTI and tTG are produced in the intestines. In fact, celiac may be the cause of some cases of autoimmune pancreatitis.

Note added in proof:

I just checked the literature on PubMed and found that PSTI is in fact an autoantigen in pancreatitis and produces antibodies against PSTI:
Raina A, Greer JB, Whitcomb DC. Serology in autoimmune pancreatitis. Minerva Gastroenterol Dietol. 2008 Dec;54(4):375-87.

I found that pancreatitis is often found associated with celiac (gluten intolerance):
Patel RS, Johlin FC Jr, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc. 1999 Dec;50(6):823-7.

Marchbank T, Weaver G, Nilsen-Hamilton M, Playford RJ. Pancreatic secretory trypsin inhibitor is a major motogenic and protective factor in human breast milk. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G697-703.

11 comments: said...

Sorry to ask what is surely a very ignorant question here in this technical discussion, but for a lay person like me, do you and your wife have any insights on whether milk and dairy products are healthful foods for humans? I tend to think that dairy products are not good choices.

Dr. Art Ayers said...

I think that milk, that is commercial cow's milk, is naturally full of compounds that are active in protecting against pathogens and establishing a particular gut flora. Unfortunately the calf's gut is not the same as the human gut. It is possible that cow's milk may be supporting a change in gut flora that is not particularly healthy for most humans. It may, however, be an improvement for some people.

I would say that the long traditional use of fermented dairy products indicates that most are healthy. Butter, for example, has fats that are much safer than the typical vegetable oil, since milk is lower in inflammatory omega-6 oils.

Many proteins in milk produce an immune response in humans. This probably only occurs in individuals with high chronic inflammation and inflammatory gut flora. This is a problem with cow's milk-based formulas, Because formula is inflammatory and supports the development of lots of allergies.

Cow's milk should be ok, but with typical inflammatory diets, it may be a problem.

I hope that this vague answer is helpful.

Thanks for the questions.

Anna said...

Also, consider that most Western people consume commercial milk that is extremely processed and adulterated (though they don't realize it). Fat and fat soluble vitamins are removed; dry milk solids are added to improve "mouthfeel" and make up for the missing fat, but that makes the protein content too high; pasteurization (UHT especially) denatures destroys the probiotics and enzymes (lipase, lactase, and phosphatase especially) that facilitate digestion and nutrient absorption; etc. Commercial milk simply isn't the same food that some pastoral human societies traditionally consumed the past 10,000 years or so.

While I wouldn't ever argue that dairy is absolutely necessary for good health (clearly much of the human population did great without it), IF dairy is consumed, well-produced (on pasture, no CAFO-produced) raw or gently home-heated dairy foods (cow, goat, sheep milk, etc.) are a better choice than the conventional industrially processed dairy foods. Reports of food-borne illness from raw milk, while possible as with any food, are greatly over-hyped and extremely rare and localized (unlike illness from pasteurized dairy foods) if the milk is produced, handled, packaged, and stored with care.

Our family has been drinking raw milk (cow and goat) for nearly three years (and I make fresh cheeses and other cultured items with it, too). We would drop milk from our diets (probably not grass fed aged cheese, butter, and heavy cream, though) if we lost access to the raw milk. Our son never liked drinking milk anyway, until we made the switch to raw milk.

And I have met the owner and toured the pasture-based farm and creamery that produces our raw milk and am satisfied that he produces a safe and wholesome product. I find conventional dairies have a "lack of transparency issue" when it comes to questions about how their products are produced.

Dr. Art Ayers said...

You have brought up many of the real issues with using cow's milk as human food. And this just starts the very broad discussion of processed vs. slow food.

The central problem of the corn/soy agribusiness system that dominates the US economy promotes unhealthy diet, energy, transportation, carbon footprint decisions. Local, small scale production is the answer.

When I taught microbiology, I would demonstrate the antibacterial properties of raw cow's milk, by spiking it with E. coli and following the death of the bacteria by dilution and plating. Also, raw cow's milk is still used in some areas of the world to decontaminate pruning tools used in orchards to prevent the spread of viruses and bacteria.

Milk is very complex and there are new research initiatives to determine the molecular structures of the oligosaccharides present in human milk.

Thanks for your interesting comments.

Muhammad Ali said...
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Muhammad Ali said...
This comment has been removed by the author.
Muhammad Ali said...

Hi Dr Ayers,

In simple language, do you mean that use of cows milk can prevent pancreatitis?

I had a bout of acute pancreatitis about 5 months ago which was attributed to alcohol abuse.

Can milk prevent even alcohol induced pancreatitis?

Dr. Art Ayers said...

Muhammad Ali,
The article I discussed was about a milk component that can inhibit the action of enzymes produced by the pancreas. Unfortunately, drinking milk with a protease inhibitor will not protect the pancreas, because the milk inhibitor will not move up to the pancreas.

My advice would be to shift to the anti-inflammtory diet that is recommended at the top of this page and reduce alcohol consumption.

Muhammad Ali said...

Dr Ayers,
Thank you for your reply. You say "reduce" alcohol consumption and not "quit" drinking. Is it safe to drink alcohol in moderation - say 180 ml of whiskey in a week - after one has had an attack of acute pancreatitis? My gastroenterologist asked me to stop drinking completely because my pancreatitis has become sensitive to alcohol owing to the bout of pancreatitis I had.

I hope the following link will be of interest to you:

jean said...

In the late 40's and 50's breast feeding was not promoted. How did those of us who received baby formula even survive? Are we more prone to pancreatitis, etc.?
I'm pretty sure the milk I received was pasteurized since Mom was extremely conventional.

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