GS and The Internet?

Here's another newsletter I found at www.gilbertssyndrome.org.uk.  Interesting info about coffee too...

Newsletter July 2006

Contents:

• Letter from the Editor.
• Is the internet damaging your health?
• Toxins and liver processing in GS.
• Is coffee good for your liver?
• Savor the richness.

Please note that contributions are not necessarily the views of Action on Gilbert’s Syndrome, and the authors are not medically qualified.

Letter from the Editor

If there’s a theme in this edition it’s that a little knowledge can be a dangerous thing, but at the end of the day some information helps you make better choices!  So, we look at how you can tell whether some of the online information you may find is up to scratch.  Plus, I have reproduced an article into the processes of the liver and in particular how they relate to cancer causing chemicals.  Research can tell us more about the processes, but doesn’t always offer us conclusions.  As the final article, on coffee, suggests.

As ever, I am here to give you information and insights as I find them.  I hope they’re interesting and useful along the way.  As I always say, I’m not medically qualified. I’m just a GS sufferer with an educated interest to share with you.

Best wishes

Adina Farmaner

Director

Is the Internet damaging your health?

Cyberspace can be an amazing source of medical information, but only if it’s used the right way.  ‘Cyberchondriacs’ are the new breed of worriers diagnosing themselves at the click of a mouse.

When we are ill -- or when we think we are -- it's on the Internet that our imaginations can really run riot.  No one is sure how many web sites are devoted to health, but it is estimated to exceed 250, 000, with some attracting up to 3 million visitors a month.  What is alarming is that they are entirely unregulated and can be written by anyone -- doctors, pharmaceutical companies or unqualified amateurs.  Add the huge number of different media messages about health and it's no wonder we are confused and, in some instances convincing ourselves that we are ill when we are not.  In fact experts have coined the term ‘cybercondriac’ for the new breed of extreme worriers diagnosing themselves at the click of a mouse.

It is natural to have concerns about our health.  But self-diagnosis via the Internet can never replace seeing an expert for individual advice.  “ So-called online or e-mail consultations are little more than electronic questionnaires and can never equate to the real thing,” says Dr Paul Cundy of the British Medical Association's general practitioners IT committee.

However, it’s after a proper diagnosis has been made that the net can come into its own.  There's a huge online support network for those with long-term illnesses or who have to have operations, as Jennifer Childs, senior information development nurse with the charity CancerBACUP explains. “A well-informed website allows those with a long-term or terminal disease to access a wealth of clear, accurate, up-to-date information, in their own time and at their own speed.  Finding information on a reputable site is supportive.  It gives people some peace of mind to know they are doing everything they possibly can to help themselves or their loved ones.”

How to assess the website’s worth.

According to the British Medical Association, you should ask the following questions when selecting a Web resource for health information:

1) is the site regularly updated?  Information on the review process, for example most recent review date, should be given on the site.

2) does the site give references and sources for the information it provides? 

3) does the site provide information about who (the organisation or individual) compiled it?  Does the organisation give an address or any other contact details? 

4) are there spelling and grammatical mistakes?  More than a couple of these indicate a weak site that has not been properly edited or reviewed.

5) is it trying to sell something?  If so, it's more likely to be biased and, therefore, best avoided.

6) books worth reading if you want to search the web include The Patient's Internet Handbook by Robert Kiley and Elizabeth Graham (Royal Society of medicine press, £9.95) and the Good Web Guide: Health by Jenny Newer (the good Web guide, £12.99).

7) the health on the net foundation (visit hon.ch) is a not-for-profit organisation based in Switzerland.  It was established to guide patients and medical practitioners to useful and reliable online medical and health information.  It has produced a simple code of conduct for medical and health websites which is worth consulting if you use the Internet regularly.

‘Click here’ for the most reliable sites:

NHS direct online provides useful and practical health information, including its own online health encyclopaedia.  You can also e-mail enquiries to resident expert.  Visit www.nhsdirect.nhs.uk for more.

Best Treatments is an NHS site that provides clinical evidence from the British Medical Journal on treatments for a wide range of medical conditions.  Visit www.besttreatments.co.uk for more.

Dr Foster is an independent organisation with a panel of leading medical experts.  It gives information on health services and treatment options, with guides on breast cancer, diabetes, infertility, obesity, adult chronic pain management and heart disease, among others.  Visit www.drfoster.co.uk for more.

Patient net is compiled by GPs and has more than 650 online information leaflets.  Visit www.patient.co.uk for more.

The BBC health news site has a library medical notes written by leading experts.  They provide information on a variety of symptoms and treatment.  Visit http://news.bbc.co.uk/1/hi/health/medical_notes for more.

Toxins and liver processing in GS.

This is an edited version of a paper into the process of Glucuronidation – which is a detox process in the liver affected by Gilbert’s Syndrome.  Generally this paper observes the evidence, or lack of it, that genetic variations in liver function have on susceptibility to cancer.  It concludes that cancer is most impacted by environment although genes may play a part. I’ve included some definitions in the text which I hope are of use, and at the end is an illustration of some of the terms used.  It’s very difficult to get the balance right in reproducing illegible medical research terminology, and a constructive conveyance of the meaning – I don’t like to interpret too much, as I’m not an expert, so bear with me!

Original article by Matthew A. Wallig1 Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue,Urbana, Illinois 61802 January 2004.

The enzymes that people with Gilbert’s Syndrome have less of are known as UGT enzymes. These enzymes are used in the parts of the liver which deal with substances such as bilirubin and estrogen (Bock, 1991). Despite their participation in a wide variety of reactions in this part of the liver, UGT enzymes are sometimes overlooked when the impact of genetic polymorphisms (Polymorphism means the ability to request that the same Operations be performed by a wide range of different types of things) (and hence variations in enzyme activity) among individuals and their susceptibility to cancer are discussed.

Alterations in UGT-mediated reactions in an individual due to genetic polymorphisms can have a substantial impact on metabolism by altering the flux of various intermediates, carcinogenic (cancer causing agents) and noncarcinogenic, through other detoxification pathways.  Glucuronidation has been estimated to account for _33% of all drugs metabolism by such detoxification enzymes (Evans and Relling, 1999); therefore, the impact of variations is potentially quite high.

In the past ten years or so a substantial body of literature has developed in which genotypic (see end of article for illustration) variation in detoxification enzyme systems has been investigated and then related to susceptibility to various cancers. Although much of the focus on genetic polymorphisms and their impact on toxicity and carcinogenesis has been centered on the cytochrome P450 and glutathione S-transferase groups of enzymes, UGT polymorphisms in relation to enhanced susceptibility to toxicity and cancer have received increasing attention in the past five years, as recently reviewed by Guillemette (2003). From these studies it has become increasingly apparent that variations in UGT genotype (see note at bottom of article for meaning and context), are associated with altered risk to certain cancers such as pancreatic cancer and breast cancer, to name just two (Guillemette et al., 2000; Ockenga et al., 2003).

As with polymorphisms in other detoxification enzyme systems, however, the association between genotype and cancer incidence has generally been weak or even nonexistent in many cases, and further complicated by factors such as race, prior drug therapy, concomitant polymorphisms in other enzyme systems, and—most consistently of all—smoking history (for example, Zheng et al., 2001). As has been observed with other enzyme systems, smoking history would appear to be the most consistent feature in the association between low activity genotypes and susceptibility to cancer; that is, in individuals without a history of smoking, the association between UGT genotype and cancer susceptibility is generally weak or absent while the opposite is true for smokers.

In contrast to the rapidly expanding literature addressing links and associations between genotype and cancer susceptibility, there is a much smaller body of literature addressing

how phenotypic variation in detoxification activity among individuals affects metabolism and inactivation of specific carcinogens and virtually no reports linking UGT genotype, UGT phenotype, and susceptibility to cancer. In particular, studies addressing glucuronidation among normal individuals and how that variation might predispose to toxicity or cancer are surprisingly sparse. The study by Hu and Wells is an initial step in filling this gap, for in it are data that clearly identify striking individual variations in UGT activities against the prototype carcinogen, benz(a)pyrene (BP), data that correlate convincingly individual capacity for glucuronidation with ability to decrease bonding and chemical toxicity of carcinogenic BP metabolites.

For their model Hu and Wells use lymphocytes from twelve normal human volunteers to assess the overall capacity of these individuals to metabolize BP, glucuronidated by UGT. Besides finding wide variation in glucuronidation (up to 200-fold) among individuals, the authors discovered strong negative correlations between the capacity to glucuronidate and/or the amount of bonding and the degree of chemical toxicity by toxic BP intermediates.

The inevitable conclusion that they draw is that normal individuals with low glucuronidation may be at increased risk for cancer caused by polyaromatic hydrocarbons that rely on glucuronidation for inactivation. The novelty of this study is that it is not only the first direct evidence for substantial interindividual variation among normal individuals in the metabolism of BP but it also confirms findings in animal models that glucuronidation can indeed modulate and presumably protect tissues from damage by reactive BP metabolites.

As in any good study, the results of this particular work pose as many questions as they provide answers. For starters, specific UGT polymorphisms were not delineated in the individuals studied and hence potential associations, correlations, and links between genotype and phenotype were not identified, something that is very much lacking in the literature overall. In addition, the various the cytochrome P450 and glutathione S-transferase phenotypes of the individuals in this study were not assessed, leaving open the question of the impact multiple polymorphisms on the responses of the various individuals to the BP metabolites. Indeed, there is evidence that polymorphisms and the subsequent variations in phenotype in several enzyme systems, rather than any one system alone, may be the most important determinant of susceptibility to cancer (Dialyna et al., 2003). Nevertheless, the findings of Hu and Wells open up exciting possibilities in the efforts to accurately determine individual risk from exposure to carcinogens.

Note re. genotype and phenotype: The genotype is the specific genetic makeup (the specific genome) of an individual, in the form of DNA. Together with the environmental variation that influences the individual, it codes for the phenotype of that individual. Non-hereditary mutations are not classically understood as representing the individuals' genotype. Hence, scientists and doctors sometimes talk for example about the (geno)type of a particular cancer, thus separating the disease from the diseased. With careful experimental design, one can use statistical methods to correlate differences in the genotypes of populations with differences in their observed phenotype. These association studies can be used to determine the genetic risk factors associated with a disease. They may even be able to differentiate between populations who may or may not respond favorably to a particular drug treatment. Such an approach is known as personalized medicine.

REFERENCES

Bock, K. W. (1991). Roles of UDP-glucuronosyltransferases in chemical

carcinogenesis. Crit. Rev. Biochem. Mol. Biol. 26, 129–150.

Dialyna, I. A., Miyakis, S., Georgatou, N., and Spandidos, D. A. (2003).

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung

cancer risk. Oncol. Rep. 10, 1829–1835.

Evans, W. E., and Relling, M. V. (1999). Pharmacogenomics: Translating

functional genomics into rational therapeutics. Science 286, 487–491.

Guillemette, C. (2003). Pharmacogenomics of human UDP-glucuronosyltransferase

enzymes. Pharmacogenomics J. 3, 136–158.

Guillemette, C., Milliken, R. C., Newman, B., and Housman, D. E. (2000).

Genetic polymorphisms in uridine diphospho-glucuronosyl transfersae 1A1

and association with breast cancer in African Americans. Cancer Res. 60,

950–956.

Hu, Z., and Wells, P. G. (1994). Modulation of benzo(a)pyrene bioactivation

by glucuronidation in peripheral blood lymphocytes from rats with a genetic

deficiency in bilirubin UDP-glucuronosyltransferases. Toxicol. Appl. Pharmacol.

127, 306–313.

Ockenga, J., Vogel, A., Teich, N., Keim, V., Manns, M. P., and Strassburg,

C. P. (2003). UDP glucuronosyltransferase (UGT1A7) gene polymorphisms

increase the risk of chronic pancreatitis and pancreatic cancer. Gastroenterology

124, 1802–1808.

Taningher, M., Malacarne, D., Izzotti, A., Ugolini, D., and Parodi, S. (1999).

Drug metabolism polymorphisms as modulators of cancer susceptibility.

Mutat. Res. 436, 227–261.

Zheng, Z., Park, J. Y., Guillemette, C., Schantz, S. P., and Lazarus, P. (2001).

Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with

orolaryngeal cancer risk. J. Natl. Cancer Inst. 93, 1411–1418.

Is coffee good for your liver?

By MEGAN SCOTT , Associated Press (ASAP)

© June 13, 2006

Some swear a cup of coffee is the best hangover cure. But could drinking regular cups protect your liver from alcohol's poisonous effects?

In a new study of more than 125,000 people, researchers found that coffee reduced the risk of cirrhosis of the liver by as much as 80 percent. Cirrhosis, an irreversible scarring of the liver, kills more than 27,000 Americans a year and sends nearly 400,000 to the hospital.

Researchers say the findings, which were published Monday in Archives of Internal Medicine, could explain why some livers survive heavy drinking. They also build on reports that coffee may reduce the risk of liver cancer.

asap spoke to Carla K. Johnson, the AP writer in Chicago who reported on the study.

What were the highlights of this study?

Johnson: The study found that people who drink an average of one cup of coffee a day cut their risk of alcoholic cirrhosis by 20 percent. People who drank four cups per day reduced their risk by 80 percent. The results were true for men and women of various backgrounds of all ages.

What kind of coffee? Folgers? Starbucks? Caffeinated? Decaf?

Johnson: The study didn't ask people what kind of coffee they drank. It just said do you drink coffee? The researchers don't know whether it's the caffeine in the coffee, antioxidants, or some other thing in coffee that helps the liver.

What about tea?

Johnson: In this study, researchers didn't see the same effect as tea. It's not clear to the researchers whether tea doesn't have whatever magic ingredient coffee has, or if it's because people drink less of it.

There so many mixed messages on coffee. What is the verdict now?

Johnson: The people I talked to say coffee's overall effect seems to be either neutral or beneficial. You don't need to feel guilty about drinking a cup of coffee, or two or three. Other studies show coffee reduces the risk of diabetes, gallstones, suicide. Watch your own consumption and see if it's causing distress to your stomach or keeping you up at night. Now alcohol on the other hand...

What are the implications of the study?

Johnson: I think the researchers may figure out what is it about coffee that seems to be helpful to the liver. Nobody is saying it's okay to drink large amounts of alcohol as long as you drink coffee. They very specifically say if you are worried about cirrhosis of the liver, you need to stop drinking. Alcohol cirrhosis is very serious. It can kill you.

Megan Scott is an asap reporter based in New York. ___

Ed. Although this is an interesting comment on liver toxicity and the effect of coffee – which is an ongoing debate, I usually advise that lots of caffeine is a bad idea.  This is because it messes with blood sugar levels, and for your liver to work properly, in people with GS, you need stable blood sugar levels.  However, small amounts may well be beneficial...

Here’s a thought to be going on with, captured from a website called The Daily Motivator, which can be found at: http://greatday.com/

Savor the richness

Feel the terrain beneath your feet. Don't just speed past it or fly over it without noticing. Hold the texture of life in your hands. Immerse yourself in the details.

There is more to being alive than watching images on a screen. There is more to experience than hearing someone tell you about it.

Know life first hand. Make your own adventure, ask your own questions, and follow your own intuitions.

Stop hiding behind the excuses. There is so very much to touch, to do, to create, and to experience.

It is down on the ground, in the details and the intimacies that you will find life's exquisite flavor. Wrap yourself around the experience, and savor the richness of every morsel.

-- Ralph Marston