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I found this info online at "Action on Gilbert's Syndrome", www.gilbertssyndrome.org.uk. It has some interesting info about several supplements.
Newsletter Summer 2007
Contents:
- Letter from the Editor.
- Dave and his research, from www.gilbertssyndrome.com
- A warning anecdote about household chemicals
- Recipes to boost your liver
Please note that contributions are not necessarily the views of Action on Gilberts Syndrome, and the authors are not medically qualified.
Letter from the Editor
www.gilbertssyndrome.com provides lots of information from a US sufferer. It combines technical with anecdotal information, and has extensive notes on both. I hope the article reproduced below gives a flavour of the site.
Domestic matters complete this edition. What’s in your home and what you eat all form part of the load on your liver. Taking a little care with both can give your liver and you a healthier life.
Best wishes and happy reading
Adina Farmaner
Director
Dave’s story
This website, from Dave in the US has extensive notes on the Syndrome and its related symptoms. I’ve reproduced part of Daves’ story here, so that you can see some of the useful information on the site, and get a flavour of his approach:
In my late 20s, I was diagnosed with having Gilberts Syndrome. All my liver function tests were normal except for elevated bilirubin. I was told at the time that Gilberts Syndrome was a benign blood disorder and that no treatment was required.
After doing some research into Gilberts, I found that it is a genetic disorder that reduces the liver enzyme UDP glucuronosyl transferase (UGT) activity to about 30% of normal levels (see ref. 7,8). It occurs in 5-10% of the general population. The UGT enzyme is actually a group of enzymes that not only detoxifies bilirubin (a toxic product of the natural breakdown of red blood cells) but also many drugs, toxins, and environmental chemicals (see ref. 1). I believe the much slower removal of these toxins is what was causing the brain fog & fatigue I was experiencing.
In order to try and alleviate the brain fog and fatigue, I turned to alternative medicine. After many years and the outlay of many thousands of dollars trying almost every supplement & alternative medicine treatment out there, I feel I have finally come across some supplements that work to alleviate my symptoms.
The supplements that I’ve found worked for me are:
· Sulforaphane (broccoli extract- see ref. 6),
· Bee Propolis (very high in flavanoid content including apigenin,
chrysin, galangin, kaempferol, luteolin, pinocembrin, pinostrobin and
quercitin-see ref. 4)
· Curcumin (see ref. 9)
· Pacalite (Calcium Montmorillonite)
· Zinc Citrate
Recent research (see ref. 2) has shown that the combination of Sulforphane and Apigenin (a flavanoid found in bee propolis) increase the activity of the UGT enzyme up to 12-fold.
Recent research also has shown that Chrysin (see ref. 4), another flavanoid found in bee propolis, resulted in a 20-fold induction of the glucuronidation of bilirubin.
Curcumin has been shown to increase UGT activity up to 7-fold (see ref. 9)
Pascalite I’ve found, is great at absorbing toxins. I’ve had great success with this supplement. More info can be found at www.pascalite.com.
As noted in ref.6, sulforaphane was isolated by researchers at Johns Hopkins in the mid 1990s. Its been patented and is commercially available under a number of brand names. The one I use is Broccomax available from Jarrow. It is available at most health food stores or on the internet.
Bee Propolis is available under various labels at most health food stores. The one I use is Y & S Organics Propolis 1000 mg caps. I get mine from www.luckyvitamins.com, but it is available from a number of resellers on the internet. Just google it and many resellers will come up.
Curcumin is available under various labels at most health food stores.The one I use is Curumin 95 from Jarrow. It is an 18 to 1 extract. I get it through the internet at the site listed above.
I’ve also found that exercising regularly speeds up the removal of toxins. I hope you will find this info useful. Over the past few years, I’ve gotten a lot of info about Gilberts from discussion boards and forums on the Internet. I thought I would give something back by sharing my experience.
References:
UDP-glucuronosyltransferase (UGT) isozymes detoxify metabolites, drugs, toxins, and environmental chemicals via conjugation to glucuronic acid.
2. UGT 12x with Sulphoraphane and apigenin combo http://www.foodnavigator.com/news-by-product/news.asp?id=54191&idCat=38&k=adding-cancer-fighters 17/8/2004 - The broccoli compound sulphoraphane and apigenin, a flavonoid found in fruits like apples and cherries as well as tea, appear to work together against cancer cells, according a new research
to be published next month.
The in vitro study is part of a growing investigation into the potential synergy between different natural compounds to acheve greater protection against cancer than from one nutrient alone.
Dr Yongping Bao from the UK-based Institute of Food Research reported last year on an interaction between sulphoraphane and the antioxidant mineral selenium in inducing anticancer enzymes and inhibiting cancerous cell growth and tumour formation. The two food components
were reported to be up to 13 times more powerful when put to work together than when used alone.
In the new study, Dr Bao reports that sulphoraphane, found in all brassica vegetables, also works in synergy with the polyphenol apigenin. Apigenin is natural flavonoid present in fruits and vegetables such as apples, beans, broccoli, celery, cherries, grapes, leeks, onions, parsley and tomatoes, as well as plant-derived beverages like tea and wine.
Writing in the 9 September issue of Carcinogenesis (vol 25), Dr Bao and colleagues note that flavonoids have a number of different properties in vitro, including the induction of phase II enzymes, such as UDP-glucuronosyl transferases (UGT) and glutathione transferases (GST), two major phase II detoxifying enzymes. These enzymes delete genetically damaged cells before they become cancerous and detoxify carcinogens making them readily excretable.
Investigating the anticancer activity of sulphoraphane and apigenin in human intestinal cells, they found that apigenin induces UGT1A1 transcription four-fold. Sulphoraphane induced both UT1A1, by almost four times, as well as GSTA1 (2.5-fold) in both dose- and time-dependent manners.
The combination of sulphoraphane and apigenin resulted in a synergistic induction of UGT1A1 mRNA up to 12-fold, they write. But both compounds acted through different signaling pathways, reveals the study, allowing for the synergistic effect.
US researchers have also studied how broccolis glucosinolates and the lycopene found in tomatoes could work together to boost the cancer protection already known to be offered by each of the foods alone. This increasingly used approach aims to measure the complex interactions that take place in the overall diet rather than singling out specific nutrients.
3. Bee Propolis-very high in flavanoid (including apigenin) content http://www.lifetimehealth.com/propolis.asp
Propolis has been around for over 45 million years, and has been used by man for thousands of years. Propolis is a sticky resin, which seeps from the buds of certain trees. The bees gather propolis, sometimes called bee glue and carry it home in their pollen baskets. The worker bees then take the resinous material and add salivary secretions and wax flakes to it and use the bee propolis in two ways: firstly to reinforce the hive itself, and secondly propolis protects
the hive from bacterial and viral infection.
Chemically, propolis is exceedingly complex and contains a rich variety of potent terpenes and benzoic, caffeic, cinnamic, and phenolic acids. Propolis is very high in flavanoid content, which has been proven to account for many of the health giving benefits attributed to propolis.
Chemical Composition More than 180 compounds have been identified in propolis, and many are biologically active. Flavonoids are abundant, including apigenin, galangin, kaempferol, luteolin, pinocembrin, pinostrobin and quercitin.
Why are flavonoids so important to our health: Propolis has a high concentration of flavonoids. Flavonoids, or bioflavonoids, are a group of polyphenolic substances which are present in most plants, concentrating in seeds, fruit skin or peel, bark, and flowers. A great number of plant medicines contain flavonoids Flavonoids play an important protective role in plants.
Flavonoids are found in a variety of foods and beverages, including cranberries, peanuts, apples, chocolate, tea and red wine.
4. Chrysin- 20-fold induction of the glucuronidation of bilirubin http://dmd.aspetjournals.org/cgi/content/full/28/9/1077Induction of UDP-Glucuronosyltransferase UGT1A1 by the Flavonoid Chrysin in the Human Hepatoma Cell Line Hep G2 Thomas Walle, Yoko Otake, Alema Galijatovic, Joseph K. Ritter, and U. Kristina Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina (T.W., Y.O., A.G., U.K.W.); and Department of Pharmacology and Toxicology, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia (J.K.R.)
The UDP-glucuronosyltransferases (UGTs) have long been known to be inducible by various chemicals, including drugs, although the extent of induction in general has been modest. In the present study, we determined the ability of the dietary flavonoid chrysin to induce UGT
activity, protein and mRNA. When pretreating human hepatoma Hep G2 cells with 25 µM chrysin, the glucuronidation of chrysin itself increased 4.2-fold when measured in the intact cell and 14-fold in the cell homogenate, i.e., autoinduction. Microsomes from chrysin-treated
cells probed with specific antibodies in Western analyses showed marked induction of the UGT1A family of proteins. Isoform-specific induction of the important hepatic UGT1A1 protein was observed but not of UGT1A6 or UGT2B7. The strong induction of UGT1A1 was confirmed by Northern analyses of total RNA as well as mRNA, using a specific probe. UGT1A1 message as well as protein was detectable also in untreated Hep G2 cells. In catalytic activity assay s with recombinant UGT1A1, 1A4, 1A6 and 1A9, chrysin was found to be a high affinity substrate for UGT1A1 (Km 0.35 µM). Catalytic activity was also found for UGT1A9 and 1A6 but not for 1A4.
Further studies demonstrated a 20-fold induction of the glucuronidation of bilirubin by the chrysin-treated cells and a 7.9-fold induction of the glucuronidation of the oral contraceptive
drug ethinylestradiol, two of the best known and specific UGT1A1 substrates, demonstrating the potential importance of this induction. In view of these findings, it will be important to extend these
studies to other dietary flavonoids
5. Chrysin found in Bee Propolis
Chrysin is a natural, biologically active bioflavonoid compound extracted from many plants, honey and propolis
6. Sulforaphane info http://www.hsrmagazine.com/articles/541branded.html
Mom always said to eat those vegetables, and epidemiological studies through the years back her up, showing people who consume large quantities of fruits and vegetables have a much lower risk of developing most types of cancer. And of the different types of vegetables available, the crucifers— broccoli, cauliflower and cabbage— have been shown rich in natural substances that could support the bodys own defense systems while also suppressing tumor development. The phytochemicals in the crucifers, particularly sulforaphane, appear to offer specific anti-cancer benefits.
Since the early 1990s, more than 200 scientific studies have supported the protective effects of broccoli and its phytochemicals in particular. The bulk of the substantive research was conducted at Johns Hopkins School of Medicine. Paul Talalay, Ph.D., is the John Jacob Abel Distinguished Service Professor of Pharmacology and director of the Laboratory for Molecular Sciences at Johns Hopkins, as well as the founder of The Brassica Chemoprotection Laboratory, which
is dedicated to studying plants that may prevent cancer development.
Talalay and colleagues first isolated and identified sulforaphane, a natural compound found in broccoli, in 1992. A pair of studies published in the Proceedings of the National Academy of Sciences discussed the method in which dietary constituents may impact endogenous enzyme activity to prevent carcinogenesis.1,2 The scientific team investigated a method to measure the induction of enzymes that detoxify carcinogens (phase 2 enzymes), and surveyed the ability of Brassica crucifers to induce phase II enzyme activity. They isolated and identified sulforaphane as well as specific isothiocyanates from SAGA broccoli (Brassica oleracea italica), and
found they were able to induce detoxification enzymes, possibly explaining broccolis anti-carcinogenic activity.Sulforaphanes glucosinolate precursor, glucoraphanin, was trademarked
as SGS™ glucosinolate.
Follow-up studies have investigated SGSs ability to induce phase 2 enzyme activity in cell culture and animal models. A study using human adult retinal pigment epithelial cells found treatment with SGS markedly reduced oxidative toxicity through phase 2 enzyme induction.3 Protection persisted even after removal of SGS. Additional work by Talalay and colleagues investigated the ability of SGS to block the formation of mammary tumors in rats treated with a
carcinogen.4 The number of rats that developed tumors was reduced by as much as 60 percent, the number of tumors in each animal was reduced by 80 percent, and size of tumors that did develop was reduced by 75 percent.
In addition to identifying the mechanism of action and investigating SGSs ability to induce phase 2 enzyme activity, Johns Hopkins researchers also looked into the best source of SGS. While different varieties of broccoli varied in their levels of SGS, it was also discovered that the older the plant becomes, the lower the concentration of SGS.5 Three-day-old sprouts were found to have 10 to 100 times the level of SGS, while also having almost none of the less desirable indole glucosinolates.
Johns Hopkins holds a number of U.S. patents in the field of isothiocyanates. The first patent, covering the isolation and identification of sulforaphane and its isothiocyanates, was granted in
1995 (No. 5,411,986). Five additional patents in the Johns Hopkins portfolio include methods of preparation for preparing food products rich in glucosinolates. The most recent patent, No. 6,521,818 B1, covers the development of a chemoprotectant crucifer germplasma, designed to produce seeds and plants with desirable glucosinolate profiles.
Today, Johns Hopkins has licensed CS Agra to produce finished products covered under its scientific and intellectual property portfolio. In the dietary supplement market, CS Agra has launched Vitalica™. Each capsule contains 30 mg SGS glucosinolate.
A breakthrough in understanding the genetic basis of Gilbert syndrome was achieved in 1995, when abnormalities in the TATAA region of the promoter were identified. The addition of 2 extra bases (TA) to the TATAA region interferes with binding of the transcription factor IID and results in reduced expression of bilirubin-UGT1 (30% of normal).
8. In 1995 UGT enzyme found to be 30 % of normal in Gilberts patients http://www.wjgnet.com/1007-9327/12/2269.pdf#search=%22bilirubin-UGT1%20(30%25%20of%20normal).%201995%22
The disorder due to a defi ciency in bilirubin glucuronidation, is commonly caused by dinucleotide (TA) insertions and [TA (TA)7TAA] alleles in the promoter region of the bilirubin
UDP-glucuronosyltransferase 1 (UGT1A1) gene. This dinucleotide insertion reduces the efficiency of transcription of the gene and decreases hepatic UDPglucuronosyltransferase activity to about 30% of normal levels in homozygous subjects[6-9].
6 Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilberts syndrome. N Engl J Med 1995; 333: 1171-1175
7 Koiwai O, Nishizawa M, Hasada K, Aono S, Adachi Y, Mamiya N, Sato H. Gilberts syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-Glucuronosyltransferase. Hum Mol Genet 1995; 4: 1183-1186
8 Burchell B, Hume R. Molecular genetic basis of Gilberts syndrome. J Gastroenterol Hepatol 1999; 14: 960-966
9 Clarke DJ, Moghrabi N, Monaghan G, Cassidy A, Boxer M, Hume R, Burchell B . Genetic defects of the UDPglucuronosyltransferase- 1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias. Clin Chim Acta 1997; 266: 63-74
9. Curcumin-7x increase in UGT activity
The most striking statistically significant enhancement was seen in small intestine by curcumin (5.4x, 6.7x and 7.2x in the proximal, mid and distal part, respectively), in large intestine by curcumin (3.1x) and in liver by flavone (7.6x). -Angelicalactone and coumarin gave an enhancement in 4-NP UGT enzyme activity at all five sites investigated. The effects of the anticarcinogens on 4-MUB UGT activity are the same as observed for 4-NP UGT activity.
However, quercetin was able to induce 4-MUB UGT activity in the proximal small intestine (2.7x) and large intestine (2.2x), -angelicalactone had no effect on mid small intestinal activity and
tannic acid did not have any effect. On the other hand flavone induced distal small intestinal 4-MUB UGT activity (2.2x), whereas fumaric acid and curcumin increased hepatic activity (2.2x and 2.6x, respectively).
Are your cleaning products safe? A warning anecdote from a friend of a friend:
‘I recently had a neighbour who had to have their German Shepherd dog put down due to liver failure. The dog was completely healthy until a few weeks ago, so they had a necropsy done to see what the cause was. The liver toxic levels were unbelievable, as if the dog had ingested poison of some kind. The dog was kept inside, and when he was outside, someone was with him, so the idea of him getting into something unknown was hard to believe.
My neighbour started to go through all the items in the house. When he got to the floor cleaner, he noticed in very tiny print, a warning which stated ‘may be harmful to small children and animals’. He called the company to ask what the contents of the cleaning agent are and was astounded to find that antifreeze is one of them. Actually he was told it’s a compound just one molecule away from antifreeze.
Therefore, just by the dog walking on the floor cleaned with the solution, then licking its own paws, it ingested enough to destroy its liver. Soon after his dog’s death, his housekeepers’ two cats also died of liver failure. They also used the same cleaning product for their floors.’
The moral is that we can all fall prey to the unknown chemical load that lies around us. Keep an eye on the ingredients of products you use around the house, and you’ll have a healthier home as a result – for you, your kids and your pets!
Simple Recipes to Boost your Liver
And keep your energy levels at optimum!
Start the day with lemon squeezed into a small glass of warm water. This kick starts your liver into flushing out toxins.
Breakfast:
1) Low fat natural yoghurt with a small handful of walnuts, a handful of blueberries, a tablespoon of oats, and honey or fructose for sweetness – will give you good fats great for keeping your cells in good form and aiding blood flow, protein for energy, antioxidants to fight toxins, and probiotics for your bowels, as well as fibre to keep energy release steady. Dandelion tea or coffee will help clear your system of toxins.
2) Organic smoked salmon with scrambled eggs and wholemeal toast with grilled tomatoes provides essential fatty acids, protein, fibre and antioxidants.
Lunch:
1) Jacket potato with low fat high protein options including: cottage cheese / tuna (loose the mayo and try reduced fat salad cream or no fat French dressing) / quorn mince cooked with a tin of tomatoes, basil , and a dash of cayenne . Plus a side salad of spinach and watercress provides fibre, protein and vital vitamins and minerals. If you swap your ordinary jacket potato for a baked sweet potato you will also gain more antioxidants and a more sustained energy release.
2) Soup is fantastic for filling up and feeling full for longer. Try a tomato based bean soup for added antioxidants, fibre and protein. With a slice of wholemeal bread spread with nut butter and yeast extract you’ll include more fibre, protein and essential fats.
Dinner:
1) In a dash of sesame oil stir fry small florets of broccoli, sliced cabbage, broad beans, slices of red and yellow pepper and carrots with one or a mix of the following - cashew nuts / diced tofu /quorn chunks / lean slices of chicken or beef / tuna, with fresh ginger, and a slug of soy sauce for flavour, plus a teaspoon of miso for savoury protein. Broccoli and cabbage are excellent for the liver, and brightly coloured veg provide antioxidants, with essential fats in the sesame oil, and nausea fighting and stomach help in the form of ginger. Egg noodles or brown rice on the side add filling carbohydrates.
2) Go traditional with grilled fish, a jacket potato, boiled Brussels (or any other dark green veg), carrots and broccoli. So long as you don’t overcook the veg, or add lashings of butter you will have a healthy vitamin, antioxidant, fibre and protein rich meal that your liver will love you for.
Snacks:
Keep energy levels primed with regular snacks. Eat a portion of the following between meals, and make sure you include a glass of soya milk or cows milk in your diet for calcium and protein, perhaps for use in tea or coffee (which should be kept to a minimum as it’s an energy thief!). Drink water throughout the day to keep flushing your system.
- o Fruit : organic apples, pears and bright fruit such as berries provide fibre and energy, vitamins and antioxidants, but are best eaten with some protein to keep you feeling full for longer, try half a sliced apple with low fat cottage cheese, or a pear and a few walnuts, or a small handful of berries in a portion of low fat yoghurt.
- o A slice of toast (or crispbread if you’re not that hungry) with peanut butter and jam, or yeast extract.
- o Sliced carrot and celery with a dip such as low fat humous, or yoghurt with mint.
- o A small bowl of cereal, such as Kellogs Sustain, or bran flakes with walnuts.
Think low fat and high protein, organic fruit and veg.
Avoid coffee and cola, diet drinks, sugar and processed foods.
Within a couple of weeks you should feel brighter and maybe even lighter.
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