Re: pancreatitis

[Guest guest]

Here's an information sheet that was part of DAAIR's

Preventing and Managing Side Effects book.

M.

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PANCREATITIS

What's the Problem, and How Do You Diagnose It?

The pancreas is the gland located in the upper abdomen that secretes

digestive enzymes into the small intestine and insulin into the

bloodstream. Pancreatitis is a very serious inflammation of the pancreas

which can sometimes be fatal. A significant percentage of people living

with HIV may at some point experience this painful complication, most

often when the pancreas becomes inflamed in response to a problematic

drug. Extremely high triglycerides are another risk factor for

development of pancreatitis. Genetic tendencies toward chronic pancreatic

problems may increase the likelihood of developing this problem. Symptoms

to watch for include upper abdominal or back pain, nausea, and

vomiting.

Pancreatitis is generally diagnosed with blood tests. Amylase, a

digestive enzyme produced in the pancreas and elsewhere, will normally be

elevated with pancreatitis. The normal range for serum amylase is 60 to

160 Somogyi units/decliliter. With extreme pancreatic damage, amylase

levels may actually be too low, indicating such extensive damage that

little amylase is being produced. Increases in lipase, the fat-digesting

enzyme, are another indication of pancreatitis, and this test is usually

done along with the test for amylase. The normal range for lipase is 14

to 280 mIU/ml.

An ultrasound may also be performed. An enlarged pancreas with a distinct

border may indicate pancreatitis.

What are the Causes?

Pancreatitis in HIV+ people most commonly results from the use of the

nucleoside analogue antiretroviral drugs (nukes). It is thought likely

that this occurs due to the damage to the mitochondria in pancreas cells

that is caused by these drugs. In addition, the high level of oxidative

stress that exists in HIV disease, combined with the worsening of the

oxidative stress due to the mitochondrial damage, may greatly contribute

to the creation of pancreatitis.

Of the nukes, ddI (Videx®) appears to confer the highest risk for

pancreatitis. Other nucleoside analogues (AZT, 3TC, ddC, d4T, may also

cause pancreatitis, although much less often. Certain combinations appear

to greatly increase the risk for pancreatitis, including ddI with d4T

(Zerit®) and/or hydroxyurea (Hydrea). In a warning letter to physicians

issued by Bristol-Myers Squibb, it is stated that ddI, d4T, and

hydroxyurea should be suspended in those with suspected pancreatitis;

that reinstitution of d4T and/or hydroxyurea after a diagnosis of

confirmed pancreatitis should be undertaken with caution; and that ddI

should be permanently discontinued in patients with confirmed

pancreatitis. The ddI package insert warns that individuals with risk

factors for pancreatitis should use the drug with extreme caution and

only if clearly indicated.

Some of the known risk factors for pancreatitis include (1) history of

pancreatitis (2) ongoing alcohol abuse (3) morbid (disease-causing)

obesity (4) hypertriglyceridemia (increased blood fats) (5)

cholelithiasis (gall stones) (6) endoscopic retrograde

cholangiopancreatography (dye test of bile ducts and pancreas gland) (7)

other medications known to cause pancreatitis; and (8) medications known

or thought to increase exposure to ddI (for example, hydroxyurea/Hydrea

or tenofovir/Viread®). Of these, the sky-high triglycerides caused most

often by protease inhibitors may be the most common additional risk

factor in HIV+ people. It is thought that drinking any level of alcohol

while taking ddI, ddC, or d4T, with or without hydroxyurea, can increase

the risk of pancreatitis.

What are the possible treatments?

The first must for resolution of pancreatitis is immediate

discontinuation of any drugs involved in its causation. As discussed

above, ddI, d4T, and hydroxyurea should be suspended immediately in

anyone with suspected pancreatitis. Beyond that, the standard medical

treatment is sadly lacking in effective therapies. It consists of simply

putting you in the hospital, giving you intravenous fluids, stopping all

oral intake, treating the pain, and watching to see if you survive.

However, research now supports the idea that mitochondrial dysfunction

caused by antiretrovirals underlies pancreatitis, so addressing that

problem should help.

Interestingly, one of the main ways in which the mitochondria can be

supported is via the use of antioxidants. Well before the theories about

mitochondrial dysfunction as a cause of pancreatitis surfaced, a number

of studies had established that with both acute and chronic pancreatitis

there is an increase in free radicals, those lethal little molecules that

are already present in high amounts and causing so much damage in HIV+

people. Researchers who have studied this believe that the free radicals

are involved in the development of pancreatic tissue damage. German

researchers have reported significant success in reducing the mortality

rate from pancreatitis with the use of antioxidant therapies to counter

the free radicals.

Key Therapies

Antioxidant therapy. There are a number of studies that support the

use of antioxidants, delivered either in intravenous solutions or orally,

for the treatment of pancreatitis. In one study of 330 people diagnosed

with acute pancreatitis utilizing CAT scans, selenium in the

water-soluble form of sodium selenite was very effectively used.

Immediately after the diagnosis, 200 mcg of selenium was given

intravenously in a bolus, followed by 800 mcg delivered over the next 24

hours. After this first day, a daily dose of 500 mcg of selenium was

given. Compared to the previous norm, the mortality rate, the rate of

complications, and the need for surgery decreased dramatically. Only 8 of

the 330 patients died. The researchers note that complications occurred

when the selenium dosing was delayed.

In another study of 99 patients with acute pancreatitis from different

causes treated over a seven-month period, using selenium in doses from

200 mcg to 1,000 mcg daily along with 1,600 IU of vitamin E daily was

found to be dramatically effective for reducing mortality, dropping the

rate of death to 1.1 percent, compared to a previous average of 34

percent. This was an effective therapy regardless of the cause of the

pancreatitis (alcohol-induced, idiopathic, post-traumatic,

post-operative, etc.).

In another smaller study by the same researchers, none of the eight

people with acute necrotizing pancreatitis who were given 500 mcg of

sodium selenite (a liquid form of selenium) died, while 89 percent of

those in the control group did. The researchers found that serum calcium

levels normalized within 24 hours of beginning the therapy, while levels

of oxidative stress markers decreased. Other studies have also shown less

mortality, faster recovery, less pain, and shorter hospital stays in

people suffering from pancreatitis who were given various forms of

antioxidant therapy, including not only selenium and vitamin E but also

vitamin C and N-acetyl-cysteine to raise glutathione. There have also

been fewer relapses in those given antioxidants. Researchers have pointed

out that the antioxidant therapy should be started as early as possible

since the free radicals are generated early in the process of

pancreatitis development.

We would note that the even better strategy is to use appropriate

supplementation of a broad spectrum of antioxidants throughout the entire

course of HIV disease, thus maintaining optimal levels of these important

nutrients in the body at all times. There are many potential benefits

from this. A decreased incidence of pancreatitis and lessened severity

when it does occur may be among them. Adding to the antioxidants the B

vitamins and carnitine that are also protective against mitochondrial

damage would also be important. The best approach is definitely to

combine all these nutrients, rather than just choosing one. Please refer

to the Mitochondrial Support and Protection Against Oxidative Stress

section of the Introduction, for NYBC’s recommended

protocol.

Glycyrrhizin. A licorice root extract known as glycyrrhizin, which

comes in both capsule and sterile IV liquid forms, the IV form has been

shown in clinical use in Japan to reverse pancreatitis, as well as having

activity against hepatitis B, CMV and HIV. Japanese researchers also

report that glycyrrhizin works as a potent anti-inflammatory and

antioxidant, both of which would help counter pancreatitis. Using either

the IV form or the oral form in combination with other antioxidants may

prove helpful.

Magnesium. Researchers have established that people with acute

pancreatitis who have low blood levels of calcium frequently have

magnesium deficiency, even though their blood levels of magnesium will

appear normal. These researchers suggest that the magnesium deficiency

may contribute to the creation of the lowered blood calcium. It is well

known that with magnesium deficiency, in general, the body will be unable

to restore calcium levels until magnesium is normalized. Supplementation

with magnesium (250 to 300 mg, twice daily) and calcium (500 mg, twice

daily) would certainly seem an appropriate accompaniment to the

antioxidant therapies.

Nutritional support. Researchers at the New York University

Medical Center have pointed out strongly that appropriate nutritional

support is extremely important with pancreatitis since failure to reverse

malnutrition in those with acute pancreatitis may increase the risk of

death. They suggest that parenteral (intravenous) nutrition should be

used initially, with formulas that include fat emulsions in amounts

sufficient to prevent essential fatty acid deficiency. When eating can be

resumed, they stress that the diet should be low in fat.

Glutamine. Replenishing glutamine is also very important in the

treatment of pancreatitis. Research has shown that a leaky gut, in other

words, the damaged kind of intestines that so many people living with HIV

have, may contribute greatly to the development of systemic infection and

mutliple organ system failure in people with pancreatitis. It appears

that endotoxins escape from the gut, enter the circulation, and

contribute to the organ failure. Dutch researcher Diep D. Tran, M.D., has

suggested that future strategies should focus on the restoration of the

gut barrier function, along with reducing the number of harmful

gram-negative bacteria in the gut (so that they can't escape and cause

the systemic infection). Both human and animal studies have shown that

L-glutamine can help to restore the barrier function of the intestine

(the way it blocks the uptake of bacteria and other pathogens, improperly

digested food, and so on).

Ketotifen also appears to be protective of the cells in the

gastrointestinal tract, protecting cells in the stomach, small

intestine, and colon from toxins. In non-HIV research, it has shown some

effectiveness as a treatment for colitis, or inflammatory bowel disease.

Thus, it may also provide some protection against the damage to the

intestines commonly caused by inflammation and pathogen-produced

toxins. This could help preserve gut function and, thus, proper

absorption of nutrients, making a nutrient program more likely to

succeed. Ketotifen is available without a prescription through NYBC.

Rather than waiting for the crisis of a pancreatitis episode, the far

better approach is to use glutamine or Ketotifen consistently throughout

this disease process for all the benefits that can give, including

maintaining the health of the intestines, including not only the barrier

function but also absorption of nutrients. Glutamine also maintains

muscle tissue, providing fuel for immune cells, and maintaining immune

protection in the linings of the body via appropriate production of

secretory IgA. However, if you haven't done this, it is crucial for

glutamine to be included in any intravenous nutrition that is given.

According to Wilmore, MD, Professor of Surgery, Harvard

University, and an internationally renowned and widely published

researcher on this amino acid, glutamine should be added to a TPN

solution at a dose of 20 grams of l-glutamine per liter of solution, a

concentration which approaches its maximum solubility. Because glutamine

is not a standard addition to TPN formulas and the dipeptide which is

highly soluble isn't available in the U.S. as yet, this must be done in a

pharmacy with the proper facilities to prepare the TPN solution.

Alternatively, the solution can be manufactured by a home care company

that makes TPN (for example, Coram Healthcare) and the solution can be

brought into the hospital. Dr. Wilmore says that the usual person with a

moderate illness needs about 30 grams of glutamine per day which is

compatible with 1.5 or so liters of TPN per day. He also notes that

additional glutamine would not be harmful as long as there is reasonably

good renal and hepatic function.

Since a number of people have reported difficulties in obtaining

glutamine to add to their IV solutions, note that TPN solutions

containing glutamine are available through Coram Healthcare, a large

company that provides home infusion therapies, and other alternate site

healthcare services. There are 88 Coram locations across North America,

including in most U.S. states as well as in Ontario, Canada. Although

only a few of their facilities can make up the TPN solution, there is no

need to have a facility near you. The only requirement is for a physician

to call in a prescription for the TPN formula; it can then be prepared at

one of the main facilities, and shipped via Fed Ex for next-day delivery.

The contact info for Coram is as follows:

Coram Healthcare’s main toll-free number for information is .

Coram Healthcare’s main website is:

http://www.coramhc.com At this

website, choose Branch Locations to locate the list of Coram

facilities.

Dietary changes. When the person with pancreatitis has recovered

sufficiently to again begin eating, it will be very important to choose

foods that will be the least stressful to the pancreas. Avoiding fried

foods, or any other high-fat, difficult-to-digest foods is crucial. It is

best to stay away from fast foods and other highly processed foods.

Instead focus on fruits, vegetables, and rice or other non-gluten

containing grains (millet, quinoa, buckwheat). Foods such as the

dark-skinned berries (blueberries, boysenberries, dark cherries,

blackberries) and the dark yellow or orange fruits and veggies (butternut

squash, pumpkin, and carrots) are relatively easy to digest and can be

soothing sources of a potent amount of antioxidants and natural

anti-inflammatories.

Pancreatic enzymes. When eating food is resumed, it will be very

important to take pancreatic enzymes with all meals and snacks. This will

reduce the demand on the pancreas to produce these, and help ensure

proper digestion when the pancreas is still not functioning properly. It

will usually be helpful to take 2 to 6 tablets with each meal. If pain is

felt in the next few hours after eating, it may also help to take an

additional 1 to 2 tablets at that time. NYBC’s Plant UltraEnzymes

are an excellent digestive enzyme, since they are from vegetable

sources and is active in a wide pH range.