Living With Endometriosis

Omega fatty acid balance can alter immunity and gene expression
By Nick Zagorski
American Society for Biochemistry and Molecular Biology
Appearing in the June 5, 2009 issue of the Journal of Biological Chemistry (JBC)

For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.

Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.

Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.

This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.

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From the article: Effect of dietary fatty acids on inflammatory gene expression in healthy humans, by Kelly L. Weaver, Priscilla Ivester, MIchael C. Seeds, L. Douglas Case, Jonathan Arm and Floyd H. Chilton
Article Link: http://www.jbc.org/cgi/content/abstract/M109.004861

Corresponding Author: (Ski) Floyd H. Chilton, III, Ph.D., Director, Wake Forest and Brigham and Women’s Center for Botanical Lipids, Winston-Salem, NC; Tel: 336.713.7105, email: schilton@wfubmc.edu

As seen on Jeanne’s Endo Blog:

Pepperoni Pizza And Pelvic Pain
Article Date: 14 Sep 2008 - 11:00 PDT

What’s the worst that could happen after eating a slice of pepperoni pizza? A little heartburn, for most people.

But for up to a million women in the U.S., enjoying that piece of pizza has painful consequences. They have a chronic bladder condition that causes pelvic pain. Spicy food — as well as citrus, caffeine, tomatoes and alcohol — can cause a flare in their symptoms and intensify the pain. Researchers had long believed the spike in their symptoms was triggered when digesting the foods produced chemicals in the urine that irritated the bladder.

A surprising new discovery from Northwestern University’s Feinberg School of Medicine reveals the symptoms — pain and an urgent need to frequently urinate — are actually being provoked by a surprise perpetrator. It’s the colon, irritated by the spicy food, that’s responsible. The finding provides an explanation for how the body actually “hears” pelvic pain.

The discovery also opens up new treatment possibilities for “painful bladder syndrome,” or interstitial cystitis, a condition that primarily affects women (only 10 percent of sufferers are men.) During a flare up, the pelvic pain is so intense some women inject anesthetic lidocaine directly into their bladders to get relief. Patients typically also feel an urgent need to urinate up to 50 times a day and are afraid to leave their homes in case they can’t find a bathroom.

“This disease has a devastating effect on people’s lives,” said David Klumpp, principal investigator and assistant professor of urology at the Feinberg School. “It affects people’s relationships with family and friends.” Klumpp said some women who suffer from this become so depressed, they attempt suicide.

Klumpp conducted the study with postdoctoral fellow Charles Rudick. The paper is published in the September issue of Nature Clinical Practice Urology.

The Northwestern researchers discovered the colon’s central role in the pain is caused by the wiring of pelvic organ nerves. Nerves from this region — the bladder, colon and prostate — are bunched together like telephone wires and plug into the same region of the spinal cord near the tailbone.

People with interstitial cystitis have bladder nerves that are constantly transmitting pain signals to the spinal cord: a steady beep, beep, beep.

But when the colon is irritated by pepperoni pizza or another type of food, colon nerves also send a pain signal to the same area on the spinal chord. This new signal is the tipping point. It ratchets up the pain message to a chorus of BEEPEEPBEEPBEEP!

“It was known that there was cross talk between organs, but until now no one had applied the idea to how pain signals affect this real world disease, how the convergence of these two information streams could make these bladder symptoms worse,” said Klumpp, who also is an assistant professor of microbiology-immunology at the Feinberg School.

The findings suggest the bladder pain can be treated rectally with an anesthetic in a suppository or gel. Another possibility is an anesthetic patch applied to pelvic skin. Studies in back pain show anesthetic patches applied to the skin can reduce back pain, Klumpp said.

“We imagine a similar kind of patch might be used to relieve pelvic pain, which might be the best solution of all,” he noted.

HOW THEY “CAUGHT” THE COLON

For the study, Klumpp and Rudnick created a model of a mouse that mimicked an inflamed bladder with pelvic pain. Then they injected lidocaine into the bladder. The pain vanished. Next they injected lidocaine into the uterus. There was no diminishment of the pain. Lastly, they tried lidocaine in the colon.

“In the colon it knocked down pain just as effectively as if we put it in the bladder. We thought if the colon can suppress bladder-associated pain, maybe it can make it worse in the way that foods irritate bladder symptoms,” Klumpp explained.

So, Klumpp injected a small dose of red pepper into the colon of a normal mouse. The injection didn’t provoke any pain. But then he injected a small dose into a mouse with pelvic pain. The pelvic pain worsened.

“We likened it to what happens to humans,” Klumpp said. “Pepperoni pizza does nothing to most people other than heartburn, but when you give it to a person with an inflamed bladder, that will cause their symptoms to flare because the nerves from the bladder and bowel are converging on the same part of the spinal cord.”

MEASURING PELVIC PAIN IN A MOUSE

When pain emanates from a visceral organ, the pain message is delivered to the spinal cord and bounces out to the corresponding skin surface, called the dermatome. To measure pelvic pain in the mice, Kumpp prodded their pelvic skin with nylon filaments of varying thickness and stiffness, beginning with one that was as thin as a human hair. The more pelvic pain the mouse was experiencing, the more sensitive its pelvic skin to even the finest filament.

As a followup, Jeanne also posted this link, which notes:

Nerve Type that Responds to “Hot Pepper” Pinpointed
Malin SA, Christianson JA, Bielefeldt K, Davis BM. TPRV1 expression defines functionally distinct pelvic colon afferents. J Neurosci. 2009 Jan 21;29(3):743-52.
The nerve receptor that responds to hot pepper-like substances is a focus of IC research because of its potential as a pain treatment target. Called the vanilloid receptor or TRPV1, it is found on two distinct types of nerves that send signals from the colon back to the central nervous system, these researchers discovered. One type fires fast, and the other, more slowly. It’s the slow-firing nerves that respond to the hot pepper substance, capsaicin, and to two other irritators, mustard oil and acid. The fast-firing type responds very little. Because this receptor is thought to be responsible for inflammatory pain hypersensitivity in visceral organs, the unique role of these slow-firing nerves that have this receptor might be exploited to design treatments.

Thousands of Pounds of Pork Recalled: Contaminated with Dioxins
usrecallnews.com
December 13, 2008

Several firms are recalling tens-of-thousands of pounds of pork due to possible dioxin contamination after being notified by the Food Safety Authority of Ireland (FSAI) that routine surveillance tests indicated the presence of dioxin in pork products that were sent to multiple importers in the United States.

Dioxins are organic compounds that act as environmental pollutants and carcinogens. They are a byproduct of the chlorine solvents known as Organochlorides, as well as byproducts in the burning of chlorine-containing products (like PVC) and the bleaching of paper.

Dioxins build up in fatty tissues over time, allowing even low-level exposure to build up over time until it reaches dangerous levels in the human body, which can cause major health effects like cancer, severe acne, damage to the nervous system, thyroid disorders, endometriosis diabetes and many others. Some studies also show that dioxins have an effect on the sex of babies born in contaminated areas.

Ireland faces $128 million bill on pork recall
reuters.com
Mon Dec 8, 2008 5:36am EST
By Andras Gergely

DUBLIN, Dec 8 (Reuters) - Ireland worked on Monday to restart the supply of pork products after dioxin contamination caused the meat to be pulled from shelves in up to 25 countries, leaving producers facing a bill of at least 100 million euros ($128.2 million).

“There are indications from my members already that between debtors list and stock that they believe is in the system, we’re looking at a bill in the region of 100 million (euros),” said Cormac Healy, director of The Irish Association of Pigmeat Processors (IAPP). “And we’re just starting there.”

Veterinary authorities said they think only 10 of Ireland’s 500 pig farms have been contaminated by dioxin-tainted feed, but they will not allow processing to restart anywhere until every producer can prove they are using clean feed.

The Irish government on Saturday ordered the food industry to recall all domestically produced pork products from shops, restaurants and plants because of contamination with dioxin, which in some forms and concentrations, and with long exposure, can cause cancer.

Authories said 10 farms in Ireland and nine in the British province of Northern Ireland had used contaminated pig feed. Both Britain and Ireland have told consumers not to eat any Irish pork products, though the risk to public health is considered extremely low.

A total 20-25 countries may have received contaminated shipments, including France, the Netherlands and Belgium, according to Irish officials.

The IAPP said pig slaughtering would not restart in Ireland for a number of days while logistical and financial problems were addressed.

“We’re facing a major financial crisis, a major liquidity problem,” IAPP director Healy said, adding that the industry has appealed for emergency financial help from the government.

Ireland exports pig meat and related products, such as pizzas, pies and sandwiches containing pork, worth 750 million euros ($950 million) a year, 63 percent of it to the United Kingdom, according to the Irish Exporters Association.

Irish producers normally slaughter an average 10,000 pigs per day, Healy said.

Irish authorities are working on a labelling system to identify new products when pork goes back on the shelves.

“Certainly we’d be hoping that there will be product back on the shelves sometime later this week,” Aidan Cotter, chief executive of the Irish Food Board, told public broadcaster RTE.

Analysts said logistical issues could be resolved quickly and products could be back on the market by mid-week, but demand would be hit.

One Dublin-based trader said market leader Kerry Group (KYGa.I: Quote, Profile, Research, Stock Buzz), which sells the popular Denny bacon rashers and Wall’s sausages, was the only major listed Irish company affected by the recall and market reaction was very muted.

“People are clearly not that concerned about it,” the trader said. “Certainly people are not reacting to it in the market at all.”

Kerry could be faced with losses of 4 million to 5 million euros per week in the approach to Christmas, said Liam Igoe, an analyst at Goodbody Stockbrokers.

“We expect the initial logistical issues to be sorted quickly and product supply is expected to be resumed as early as tomorrow,” Igoe said in a research note.

A spokesman for Kerry Group spokesman said its products had been pulled from shelves but would not give a monetary value of the company’s potential losses.

“We’re not directly involved in the incident, we’re not involved in primary pork production,” the spokesman said.

“We’re hopeful that we can secure new supplies of raw materials and we’ll have products back on the shelves tomorrow or Wednesday.”

Shares in Kerry was trading 0.9 percent lower at 16.55 euros by 1032 GMT, underperforming a 4.5 percent higher wider Irish market .ISEQ. (Editing by Karen Foster)

Eating tomatoes may help treat endometriosis
November 12, 2008
Mark Henderson, Science Editor, in San Francisco

An antioxidant chemical found in tomatoes could be used to treat common causes of abdominal pain such as internal scarring after surgery and endometriosis, new research has suggested.

Lycopene, the bright red pigment that gives tomatoes their characteristic colour, can inhibit proteins that are linked to the formation of abnormal patches of tissue called adhesions, according to a study of cells in culture.

Though the findings are very preliminary, they hint that a diet rich in tomatoes and tomato products, or supplements containing lycopene, might be a promising way of controlling adhesions.

Adhesions are patches of scar tissue or fibrous strands that form on internal surfaces in the abdomen, often connecting two organs or parts of organs together. They are a common side effect of surgery, and they also occur in endometriosis, a condition in which tissue that normally lines the womb grows in other parts of the abdomen. These growths can cause pain, bowel obstructions, bladder problems and infertility.

Abdominal adhesions are commonly associated with tissue damage caused by free radical oxygen molecules, leading a team headed by Tarek Dbouk, of Wayne State University in Detroit, to investigate lycopene because of its antioxidant properties.

The chemical, which is particularly abundant in cooked tomato products such as ketchup and pasta sauces, is already thought to have protective effects against cardiovascular disease and some cancers.

In the study, Dr Dbouk exposed human cells to lycopene in the laboratory, and measured its effect on proteins that serve as markers for adhesion formation. Levels of these proteins were substantially reduced, by as much as 80 to 90 per cent.

Dr Dbouk told the American Society for Reproductive Medicine conference in San Francisco that the results suggest that lycopene – and tomatoes that contain it – could be useful for treating post-surgical adhesions and other conditions such as endometriosis and uterine fibroids.

“What we found in our laboratory study is that lycopene can help with the adhesions that these conditions cause,” he said. “One of the major complications of endometriosis is that it causes inflammation which induces adhesions.

“The inflammation basically causes scarring. What we did was to look at protein markers that could help us trace the activity of the abnormal cells that cause these adhesions. The lycopene worked to reduce the abnormal activity of these cells.

“This means that you would not get the adhesions, which suggests that lycopene could work to mitigate the complications and ailments of endometriosis. So, hypothetically speaking, we might be able to reduce the adhesion effects of endometriosis.”

The study does not show whether lycopene absorbed through the diet would have the same effect on real cells in the human body, but Dr Dbouk said it could be practical to get it in this way. “It is certainly possible that you could get the amount you need from your diet,” he said. “Or if the patient did not like tomatoes, you could give them the lycopene as a supplement.”

Diet Linked to Endometriosis (to view the article directly, paste the url to a google search window, then click through to the story. Otherwise, if you go to the url directly, they’ll try to make you sign in as a registered user)
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

July 15, 2004 — Dietary fruits and vegetables seem to protect against endometriosis, whereas red meat and ham seem to increase the risk, according to the results of two case-controlled studies published in the July issue of Human Reproduction.

“We found … that there was a 40% relative reduction in risk of endometriosis in women with higher consumption of green vegetables and fresh fruit,” lead author Fabio Parazzini, from the Gynaecologic Clinic of the University of Milan in Italy, says in a news release. “But, for those with a high intake of beef, other red meat and ham, there was an increase of about 80-100% in relative risk.”

The investigators compared dietary patterns in 504 women admitted to obstetrics and gynecology departments for laparoscopically confirmed endometriosis with those of 504 women admitted for acute nongynecological, nonhormonal, nonneoplastic conditions. Median age was 33 years (range, 20 to 65 years) in the cases and 34 years (range, 20 to 61 years) in the controls.

Participants were asked about their diet in the year preceding the interview, including how many weekly portions they ate of selected dietary items, including the major sources of retinoids and carotenoids in the Italian diet. They were also asked about alcohol and coffee consumption.

Compared with women in the lowest tertile of dietary intake, risk of endometriosis was significantly lower for the highest tertile of intake of green vegetables (odds ratio [OR], 0.3) and fresh fruit (OR, 0.6). High intake of beef and other red meat (OR, 2.0) and ham (OR, 1.8) were associated with increased risk.

Endometriosis was not significantly associated with intake of milk, liver, carrots, cheese, fish, whole-grain foods, coffee, alcohol, butter, margarine, or oil.

If these findings are confirmed in prospective studies, the authors suggest that attention to diet could reduce the prevalence of endometriosis from 5% in Italy to around 3% to 4% or about 200,000 prevalent cases (and about 10,000 new cases a year) fewer in Italy and 800,000 fewer prevalent cases in Europe.

Study limitations include data for only a few selected indicator foods, no estimate of portion size or total energy intake, and the possibility that a high intake of green vegetables, fruits, and fish could reflect more health-conscious attitudes and/or greater likelihood of having endometriosis diagnosed. The authors recommend prospective interventional studies to address these issues.

“However, despite these limitations, our study does suggest that there is some link between diet and risk of endometriosis and indicates that we now need a proper prospective interventional investigation to study these factors,” Dr. Parazzini says. “Endometriosis is a distressing condition that affects the quality of life for many women and if there are adjustments that can be made in the diet to lower the risk it is vital that we gain really firm evidence about which foods protect and which foods increase risk.”

The Associazione Italiana per la Ricerca sul Cancro helped support this study.

Hum Reprod. 2004;19:1755-1759

Clinical Context

Endometriosis is said to affect up to five in 100 women in Italy and Europe. Although its pathophysiology is unknown, a study by Britton and colleagues published in the May 2000 issue of Cancer Causes Control linked endometriosis with higher intake of polyunsaturated and vegetable fats, with no risk reduction associated with high vegetable and fruit intake. An inverse relationship has been shown between endometriosis and body mass index (BMI), for example, in a report by Missmer and Cramer in the March 2003 issue of Obstetrics and Gynecology Clinics of North America. There are also suggestions that the condition is related to exposure to higher estrogen levels, which also is associated with fibroids and endometrial cancer.

The authors of this study postulate that a diet high in fats increases the circulation of unopposed estrogens and may predispose to endometriosis. Fats may also influence prostaglandin concentration and affect ovarian function.

This report combines two retrospective case control studies to examine the association between dietary intake and incidence of endometriosis, relying on a single seven-day food intake recall of Italian patients presenting to hospitals.

Study Highlights

• 504 women younger than 65 years with laparoscopically confirmed endometriosis from obstetrics and gynecology departments in 3 cities were matched in 1:1 ratio to 500 age-matched hospital controls without endometriosis.
• In the control group, 31% were admitted for traumatic conditions, 23% had nontraumatic orthopedic conditions, 12% acute abdominal pain, and 34% other illnesses. Absence of endometriosis in these women was not confirmed by laparoscopy.
• Both patients and interviewers were blinded to the purpose of the study.
• Patients completed a structured questionnaire while in the hospital, on medical and gynecological history, lifetime oral contraceptive use, and food frequency diary for the last 7 days covering selected dietary intake of fats, whole-grain foods, retinoids and carotenoids, alcohol, tea, and coffee. Validity and reliability of this method was not defined or compared with other food intake assessment methods.
• Alcohol intake was defined by amount of ethanol in wine (125 mL), beer (40 mL), and spirits (15 g). Wine accounted for more than 80% of alcohol consumed.
• Recall of typical food intake for the prior few years was not recorded. Other lifestyle factors such as smoking and exercise, other gynecologic conditions, and use of hormones other than oral contraceptives was not reported.
• There was no estimate of portion size or daily energy intake.
• BMI was documented as less than 20, 20 to 23, and more than 23 kg/m2 with no separate category for overweight or obesity.
• Intake was subjectively described by patients as low, intermediate, and high for each category which was then converted to tertiles of intake for milk, meat, beef, liver, carrots, green vegetables, eggs, ham, fish, and cheese portions.
• Mean age was 33 years (range, 20 to 65 years). Women in the endometriosis group were more educated, thinner (lower BMI), and more frequently multiparous than the control group.
• There was a significant reduction in risk of endometriosis associated with high intake of green vegetables (OR, 0.3) and fresh fruit (OR, 0.6).
• Increased risk was associated with beef and other meat (OR, 2.0) and ham (OR, 1.8) intake.
• The ORs were 1.0 and 1.8, respectively, for intermediate and high intake of beef and other red meat, and 0.5 and 0.3, respectively, for intermediate and high intake of vegetables.
• These trends were still significant when age, BMI, education, and parity were taken into account.
• Consumption of milk, liver, carrots, cheese, fish, whole grain foods, butter, margarine, oil, coffee, and alcohol were not associated with endometriosis.