Polycystic Ovarian Syndrome/Endometriosis is an endocrine/immunity disorder. YES WE KNOW THE CAUSE.

The one myth that has irked me is when these "reputable" sources ie. WebMD says,

"there is no known cause".

My favorite is,

"there is no known cure".

A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS) was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 microg estrogen at 5-7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus.

The thymus is a specialized organ of the immune system. The only known function of the thymus is the production and "education" of T-lymphocytes (T cells), which are critical cells of the adaptive immune system.
http://en.wikipedia.org/wiki/Thymus

http://www.ncbi.nlm.nih.gov/pubmed/19450261?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

HELLO!!! WE HAVE OUR CULPRIT.
THIS IS EVIDENCE THAT POLY-CYSTIC OVARIAN SYNDROME(and possibly Endometriosis)IS AN IMMUNE DISORDER!!!

(and no you can cure that will birth control pills either)

BULLSh*t there's "no known cause". All fingers point to iodine deficiencies and metabolic disturbances- which affects the immune system which affects the endocrine system. This same issue causes a bunch of cancers, etc.

Baloney Maloney.

We need to challenge the medical community, give them competition to provide good information. Good information and research is out there, it's up to us to take the initiative to find it. Do we accept band-aids or a cure? The market is good for birth control pills and diabetes drugs. It's up to us to determine their financial incentive.


Here's my collection: it's lengthy. This information is yours, FREE OF CHARGE. If you want to pursue any more studies, use this as a stepping stone.

IODINE and PCOS-

the recommended dosage is 12.5-50 mg/day- in fish, seaweed, DAIRY...Americans consume an average 240 micrograms (µg) of iodine a day.
" It removes toxic chemicals — fluoride, bromide, lead, aluminum, mercury — and biological toxins, suppresses auto-immunity, strengthens the T-cell adaptive immune system, and protects against abnormal growth of bacteria in the stomach."
http://www.lewrockwell.com/miller/miller20.html

"A study of female mice is suggesting that ovarian cysts may at least partially be the result of an immune system dysfunction. The gland involved is the thymus gland, which is responsible for the management of major aspects of your immune system. One of the functions of the thymus gland is to produce T-cells, which are white blood cells that help protect you from infection and also perform other important activities.
The researchers reported that ovarian cysts in the female mice did not develop unless there was an absence of regulatory T-cells."
http://www.ovarian-cysts-pcos.com/news81.html

Iodine deficiency may cause the ovaries to develop cysts , nodules and scar tissue. At its worse this ovarian pathology is very similar to that of polycystic ovarian syndrome (PCOS). As of the writing of this article I have five PCOS patients. The patients have successfully been brought under control with the use of 50 mg of iodine per day. Control with these patients meaning cysts are gone, periods every 28 days and type 2 diabetes mellitus under control.
http://www.optimox.com/pics/Iodine/IOD-10/IOD_10.htm

OK, enough credentials (don’t want people thinking I’m just making this stuff up!), on with my notes.

Though first, a quick science lesson – on the periodic table of elements, you’ll see a row that looks like this:

F (Fluorine)
Cl (Chlorine)
Br (Bromine)
I (Iodine)

These are the halogens. Dr. Flechas will mention Bromine/bromide, Chlorine/chloride and Fluorine/fluoride in his discussion of iodine. The following will help you understand the connection.

From http://www.doctorvickery.com/IODINE.cfm:

“...There are four halogens: iodine, bromine, fluorine and chlorine. Only iodine and chlorine are necessary to the body. We need iodine in all the aforementioned tissues ( Probably all tissues but it is concentrated here). We need chlorine in the stomach for secretion of hydrochloric acid. Chloride is also an important part of the blood’s regulation of its acid-base balance. You need chlorine to breathe.

“All these halogens use the same receptors in the body. Therefore if a person’s diet is deficient in iodine the iodine receptors in the thyroid and stomach, for example, may fill up with bromine which is common in grains, bleached flour, sodas, nuts and oils as well as several plant foods. Then the person’s thyroid function is deficient and the iodide-pump in the stomach will not work efficiently either. There has been research also done on the role of insufficient iodine and breast cancer and cysts in the ovaries and uterus. A person whose sweat glands are low in iodine will have dry skin. (It is important to note that the present “low salt” regimes leave us chloride deficient as well) Fluorine from sources such as toothpaste, certain teas, and fluoridated water will also take up receptor * Censor ** Censor ** Censor ** Censor ** Censor ** Censor ** Censor *

“Once this receptor space is taken up, my research shows me that it takes a certain level of iodine loading to replace the unwanted halogens with iodine, this seems to be especially so of bromine.”

-------------------------------------------------------------------------


Here are my notes. I've added a few comments which are marked this way: <<>>

* 84% of women have some kind of cyclical breast pain, which is related to fibrocystic breast disease and linked to iodine deficiency.

* Dr. Guy Abraham, an OB/GYN and iodine researcher, reports that iodine deficiency in the thyroid = cysts, nodules, scar tissue and goiter.

* Also, iodine deficiency in the breasts = cysts, nodules, scar tissue, enlargement and tenderness (fibrocystic breast disease (FBD)).
* New England Journal of Medicine, July 24, 2005 – women with FBD have a high rate of cancer.
* Breast tissue uses iodine as much or more than thyroid
* Iodine deficiency in the ovaries = ovarian cysts, PCOS.
* Absence of iodine in a tissue will eventually lead to cancer
* A women with hypothyroidism has a 6% chance of developing breast cancer. Once she starts taking thyroid hormone, it doubles her chances. Once she’s been on thyroid hormone replacement for 15 years, it more than triples it – 19.6% chance of developing breast cancer.
* Cities/counties/states with high rates of hypothyroidism also have high rates of breast cancer.
* Thyroid hormone inhibits the body’s ability to uptake iodine.
* RDA of iodine = how much to prevent goiter, not how much our body needs to be healthy.
* Iodine in the body is used as follows: 3% by the thyroid, 70% by muscles and fat, 20% by the skin, and 7% by the ovaries.
* Absence of iodine in tissue allows cysts to grow.
* In his practice, Dr. Flechas has had women with PCOS on iodine supplementation and has seen their cycles return to every 28 days. <<>>
* Absence of iodine in early pregnancy = ADD type symptoms in children
* Adequate amounts of iodine in early pregnancy and early childhood improves intelligence.
* In China, where there is fluoride in the water and the iodine levels are marginal, many babies born are cretin.
* In the U.S., iodine used to be in bread – 160 mcg of iodine per slice of bread. Now they use bromide. Not long after this change occurred, the incidence of breast cancer rose dramatically.
* Iodine used to be in milk, but is no longer.
* 50% of American women cook with salt that has no iodine. The Journal for the AMA recommends all physicians decrease their patients salt intake by 50%. Where are these patients supposed to get iodine?
* 25-30% of those who go senile do so due to lack of thyroid hormone which is due to a lack of iodine.
* Bromides are used to make beautiful-looking loaves of bread.
* Back in the 20's, Bromo-Seltzer was used to cure headaches and hangovers. Too much Bromo-Seltzer caused a buildup of bromide which resulted in paranoia and schizophrenia, which the doctors termed “Bromomania”.
* New England Journal of Medicine reported that from 1920 to 1960, 20% of the people admitted into psychiatric hospitals had acute paranoid psychosis (Bromomania) because of Bromo-Seltzer.
* At the time, physicians would wonder if an alcoholic was going through the DT's or if the symptoms were from Bromide poisoning.
* In 1964, the FDA was concerned, so Bromo-Seltzer left the market. But, that same year, bromide was included in another produce in the form of brominated vegetable oil – Mountain Dew. They use it to disperse the citric acid in citrus- flavored drinks. <<>>
* We’re getting Bromide in bread and soft drinks. Iodine and salt can help your body release the bromide.
* Dr. Flechas used his son as one of his research subjects while he was studying iodine supplementation. They were collecting his urine to study what was being released. They noticed ½" of brown sediment at the bottom of the container. It was tested at the lab – it was bromide. They tracked down the source to the Mountain Dew he drinks.
* When bromide combines with a liquid oil, it turns it into a solid. Kids/Adults with morbid obesity can’t get rid of fat due to the tremendous amounts of bromide. <<>>
* Bromide depresses the central nervous system. They load Mtn. Dew with caffeine to make up for that effect. <<>>
* <<< I can’t remember if this is from him or if it was my thought – Bromomania is bromide poisoning which produces paranoia and schizophrenia. Mtn. Dew fills kids with bromide. Many kids drink 5 or more Mtn. Dews each day. Could this be part of the problem with the amount of paranoia in schools – the paranoia that leads to voilence and shootings??>>>
* In 2000, the Brazilian government outlawed bromine in flour.
* Bromide is injected into soil and sprayed on some fruits and veggies since it makes a great pesticide. Fluoride is also used as an insecticide and pesticide.
* In China they have found that no geniuses come from areas with fluoridated water. Many are of substandard intelligence.
* Average American gets 138 mcg (micrograms) of iodine each day. Your body can utilize 9-10 mg (milligrams) per day. 1 mg = 1000 mcg 9 mg = 9000 mcg
* PCOS = increased risk for ovarian cancer in your 40s and 50s.
* 20% iodine sits in the skin – helps the body sweat. If you don’t sweat, you may be iodine deficient.
* Japan has the lowest amount of cancer in the world, even though they’ve been bombed twice with nuclear bombs. Because they eat so much seaweed, they get the highest doses of iodine of any country. Chernobyl also had a nuclear disaster. The people there developed a lot of cancer.
* Iodine kicks the bromide out of the cells, and it ends up in the kidneys. Chloride (from salt) pushes it from the kidneys into the urine.
* In the 1920s, people were given 50 - 150 mg of iodine each day for goiter.
* For those coming to his clinic with PCOS, insulin resistance and diabetes, he’s put them on 50mg of iodine/day in the form of Iodoral. It has both iodine and iodide. Some tissues want only one or the other. Breasts like both iodine and iodide.
* One very cool example he gave is of a woman with diabetes. She arrived at the ER with very high blood sugar. They put her on insulin. When she came back 2 weeks later, to the clinic, he also put her on Iodoral because she has fibrocystic breast disease. Within a few weeks, she was complaining of hypoglycemic symptoms, and Dr. Flechas told her to reduce her insulin. Two or three months after that initial ER visit, she came in for her checkup. Her ave. bloodsugar was 98. And she had not injected any insulin for a couple weeks because of the hypoglycemic symptoms – she has slowly weaned off all insulin.
* 90% of all diabetics make insulin – they just can’t utilize it. Iodine helps the receptors work better.
* FSH/LH receptors are also helped by iodine. He mentioned that patients who aren’t having periods began having regular cycles again. <<>>
* The amino acid Histadine is the pre-cursor to Histamine (which triggers allergy symptoms like itchy, runny nose and eyes). Iodine inhibits the conversion from histadine to histamine – so it's a natural antihistamine.
* Those put on thyroid hormone may still suffer with 90% of their symptoms. For many, they have the thyroid hormone already, the problem is with the receptors <<>>.
* Neuro-hormones in the brain also benefit from iodine. Within days, some people with depression find relief.
* Dr. St. Georgie (discoverer of Vit. C.) reported that based on researchers over 100 years (1850 to 1950), the average human needs 62 mg of iodine/day.
* Dr. Flechas has been supplementing with iodine for a number of years now. It took him a year to come off his thyroid hormone for hypothyroidism.
* Less than ½ of 1% of the population is allergic to iodine.
* You can get an iodine loading test done to determine your level of deficiency.
http://www.fertilethoughts.com/forums/pcos-diabetes/506126-dr-flechas-research-linking-iodine-deficiency-pcos-ir-hypothyroidism.html

17-hydroxyprogesterone
The most common biochemical abnormality in women with PCOSis hypersecretion of androgens. The increased steroidogenic activ-ity is due to increased 3α-HSD and 17α-hydroxylase/17,20-lyaseactivities (Nelson et al., 1999; Nelson et al., 2001).
Northern blotanalysis revealed that cytochrome P450 17-hydroxylase/17,20-desmolase (CYP17) and cytochrome P450 side chain cleavageenzyme (CYP11A) mRNAs were more abundant in PCOS thecacells than in normal ones.
In addition, transient transfection exper-iments indicated that the CYP17 promoter is enhanced in PCOStheca cells compared to normal theca cells (Wickenheisser et al.,2000). The up-regulation of steroidogenesis in PCOS the ca cell suggests the presence of an intrinsic defect in the metabolic path-ways of the cells responsible for androgen production independ-ently of environmental and neuroregulatory factors. However, theca cell studies have been performed only on classical PCOS phenotype with hyperandrogenemia and there is no information if all subtypes of theca cells present a steroidogenic defect. Additional studies on theca cells isolated from different PCOS phenotypes will provide valuable information.
http://www.scribd.com/doc/7269904/PCOSObesity-Genetics-Pcos-HRU

17α-hydroxylase (or CYP17A1) is an enzyme in steroidogenesis, where it converts pregnenolone and progesterone to their 17-hydroxy forms.
The enzyme itself is attached to the smooth endoplasmic reticulum of the steroid-producing cells of the adrenal cortex and gonads. CYP17A1 functions as both a 17α-hydroxylase and a 17,20-lyase. The dual activities mediate three key transformations in cortisol and sex steroid synthesis:
• As 17α-hydroxylase it mediates pregnenolone → 17-hydroxypregnenolone
• and progesterone → 17-hydroxyprogesterone.
• As 17,20-lyase it mediates 17-hydroxypregnenolone → DHEA.
• An expected second 17,20-lyase reaction (17-hydroxyprogesterone → androstenedione) is mediated so inefficiently in humans as to be of no known significance.
• Effects of impaired sex steroid synthesis in 17α-hydroxylase deficient CAH
• Genetic XX females affected by 17α-hydroxylase deficiency are born with normal female internal and external anatomy. At the expected time of puberty, neither the adrenals nor the ovaries can produce sex steroids, so neither breast development nor pubic hair appear. Investigation of delayed puberty yields elevated gonadotropins and normal karyotype, while imaging confirms the presence of ovaries and an infantile uterus. http://www.websters-dictionary-online.com/definitions/Congenital+adrenal+hyperplasia+due+to+17+alpha-hydroxylase+deficiency?cx=partner-pub-0939450753529744:v0qd01-tdlq&cof=FORID:9&ie=UTF-8&q=Congenital+adrenal+hyperplasia+due+to+17+alpha-hydroxylase+deficiency&sa=Search#906

In female rats, diet enriched in advanced glycation end products (AGEs) has been associated with increased serum testosterone levels and deposition of dietary glycotoxins in ovarian tissue.
Women with PCOS present increased serum AGE levels, which are acutely elevated after intake of a single meal high in AGE content. In this study the effects of a hypocaloric diet and an AGE-enriched hypocaloric diet were investigated, on the endocrine and metabolic profile of PCOS women.
Eleven women with PCOS, defined by Rotterdam criteria, were assigned for two months to a hypocaloric regular diet followed by two months of a hypocaloric AGE-enriched diet. At the end of each period endocrine parameters were determined.
PCOS women on hypocaloric diet showed a significant reduction on BMI (P=0.0276), which was followed by a significant reduction on HOMA (P=0.0035), but not significant changes on AGEs (P=0.6073) or Testosterone concentrations (P=0.7857). In post hypocaloric-AGE-enriched diet, without significant changes in BMI (P=0.29) and HOMA (P=0.1560), testosterone levels (P=0.0007) were increased in comparison to their status during hypocaloric diet and to baseline. Additionally, the difference of AGEs levels from hypocaloric diet to high AGEs diet were significantly higher (P=0.0312).
Increased dietary intake of AGEs in hypocaloric diet is associated with significant increases in androgen levels, contributing to abnormal hormonal profile in women with PCOS. Since in the ovarian compartments from polycystic ovarian tissue the AGE and their receptor RAGE have been determined immunochemically, the role of dietary AGEs in PCOS needs to be explored
http://www.endocrine-abstracts.org/ea/0016/ea0016p171.htm

"Advanced glycation end-products (AGEs) are highly reactive molecules, formed by nonenzymatic glycation of proteins, lipids, and nucleic acids, which may induce structural and vascular change" (fast food-precooked foods)

"In conclusion, it is demonstrated that excess dietary glycotoxins in experimental animals appeared to be accumulated in the ovarian tissues and are also associated with metabolic and hormonal alterations.”
http://www.springerlink.com/content/g872k677v1114520/
http://www.medicalnewstoday.com/articles/169805.php

Nonenzymatic advanced glycation and oxidation end-products, advanced glycation end-products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress. Insulin resistant (IR) polycystic ovary syndrome (PCOS) women, have elevated serum AGEs, increased receptor (RAGE) expression, and increased deposition with differential localization in the polycystic ovarian tissue (theca and granulosa) compared to normal.
CONCLUSIONS: In PCOS, serum AGEs are distinctly elevated compared with women having the isolated characteristics of the syndrome. No difference was observed between PCOS subphenotypes. As chronic inflammation and increased oxidant stress have been incriminated in the pathophysiology of PCOS, the role of AGEs as inflammatory and oxidant mediators, may be linked with the metabolic and reproductive abnormalities of the syndrome. http://www.ncbi.nlm.nih.gov/pubmed/18363886

The Endos and glycotoxins http://www.ncbi.nlm.nih.gov/pubmed/19088375

AGEs are harmful substances that are abundant in Western diets, and proliferate when foods are heated, pasteurized, dried, smoked, fried or grilled. Once absorbed in the body, AGEs adhere to tissues and oxidize them, causing inflammation which in turn can lead to disease. Numerous animal studies conducted by Dr. Vlassara and her team have shown that oxidative stress from high oxidant levels and inflammation related to long-term exposure to AGEs may increase the risk of diabetes, heart disease, kidney disease and other chronic conditions.
For the study, a subset of 40 healthy participants who were either between the ages or 18 and 45 or older than 60, and another nine patients with kidney disease, were randomly assigned to one of two diets. One group followed their own regular Western diet that was rich in AGEs. The second group followed a diet of similar caloric and nutrient content, but with only one-half the amount of AGEs, known as the "AGE-less diet."
Participants in the AGE-less intervention were advised to avoid grilling, frying or baking their food and instead were instructed to poach, stew, or steam their meals. There was no change in calories or nutrient intake during this period.
After four months on the AGE-less diet, blood AGE levels, lipid peroxides, inflammatory markers, and biomarkers of vascular function declined by as much as 60 percent in healthy participants. A reduction of similar magnitude was found in kidney patients after only one month on the AGE-less diet.
http://www.sciencedaily.com/releases/2009/11/091104000929.htm

“The content of AGEs in the food is strongly influenced by the methods of preparation, particularly, the amount and duration of exposure to heat and by the associated water loss,” the study says. “Thus, methods such as frying or broiling greatly augment the AGE content of common foods, compared to boiling and steaming.”
http://www.healthcentral.com/diabetes/c/17/8985/ages-arent-aged

ON AGEs

Dear Reader,
Maybe you’re like me and you like your steak bloody or at least still pink in the middle. Let me put your mind at ease. The idea that it’s “healthier” to cook meat until it’s dry and tasteless is not backed by real scientific fact. In fact, cooking your food that way can cause arthritis, cancer, diabetes and heart disease.
Overcooking denatures protein, breaks down vitamins and removes nutrients. And, new research studies have linked eating these foods to premature aging by a process called glycation. Glycation is what happens to the proteins in our body as we age. The same process turns a turkey’s skin brown and crispy when it’s cooked.
Glycation is really the binding of protein and glucose molecules. The result is glycotoxins. As the glycotoxins accumulate in your cells, they send out chemical signals. The body responds by producing sites of inflammation. In addition, the abnormal protein structures do not regenerate.

They remain damaged. This is the process of aging and disease.

When we overcook foods, large amounts of glycotoxins collect in the food. A new study demonstrated that if we eat these foods, the glycotoxins transfer to our tissues.

Researchers at the Mt. Sinai School of Medicine evaluated 24 diabetic participants. Scientists split the subjects into two groups. One group ate a diet low in glycotoxins. The other group ate a diet high in glycotoxins.
After only 2 weeks, the group eating the high-glycotoxin diet had up to 100% more glycotoxins present in their blood and urine that those who ate the low-glycotoxin diet1.
This is clear evidence that the glycotoxins from your food transfer into your body.
Overcooking has another negative consequence. It denatures many important nutrients in food. One of the best examples is CoQ10. You need CoQ10 for proper functioning of all of the major organs in your body. The best source of CoQ10 is red meat. Overcooking meat destroys CoQ10.
The good news is that by changing a few cooking habits you can enjoy good food, without glycotoxins. You can also add a supplement to your routine that helps fight glycation.
High-heat cooking methods usually cause food to change color or consistency. But if you want to avoid premature aging, try some different techniques.
You can reduce the number of glycotoxins in your food by cooking it at a lower heat. But low heat doesn’t have to be low in taste. You can use spices and fresh herbs to boost the taste of meals cooked at lower heat. Marinating your meat before you cook it is another good way to prevent or slow glycation.
The only supplement proven to prevent glycation is carnosine. A recent laboratory study shows that carnosine plays a direct role in disposing of glycated proteins in your tissues2. About 1000-mg of carnosine daily should protect your body from being cooked from the inside, out. Carnosine also protects your muscles from degenerating.http://www.alsearsmd.com/like-your-steak-rare/

Glycation Cross-linking

Cross-linking of proteins by glycation products reduces flexibility, elasticity and functioning of proteins, and can initiate harmful inflammatory and autoimmune responses. Thus is it implicated in degenerative diseases, and wreaks havoc on all body tissues, including:

1. •collagen in connective tissue,
2. •collagen in arterial tissues,
3. •kidneys,
4. •lens of the eye,
5. •immune cells,
6. •nerve myelin proteins,
7. •circulating LDL in the blood. 6


Anti-Glycation Response: Inflammation

Just as with oxidation, the immune system of healthy individuals is equipped to deal with AGEs. White blood cells known as macrophages each have hundreds of receptors to bind AGEs, allowing the macrophage to digest these toxic products. Just as when macrophages digest oxidized LDL products, foam cells are formed to contain the toxic material until HDL can remove it to the liver for further detoxification. But if there is insufficient HDL for the task, the foam cells will eventually burst, releasing their highly toxic contents to do further damage. In this way the inflammation is propagated.


What can Curb the Glycation Spiral?

The pharmaceutical companies are busy looking for drugs to solve the problem. Already, the drug Aminoguanidine, under the brand name of Pimagedine is being studied for it’s ability to slow the formation of glycation-induced crosslinks. And it has been proposed that aspirin may also have this ability (for example, chronic users of aspirin have fewer cataracts). Research is also underway to find drugs that will break the AGE crosslinks that have already formed. 3

Dr Nicholas Perricone believes he has found a natural solution. He proposes a low carb diet to normalize blood sugars (the same as that used to curb the oxidative spiral), along with supplementation by specific polysaccharides * and neuropeptides, as well as vitamins and other natural food-derived substances known to have anti-glycation function. 4

[* NOTE: While these polysaccharides are made up of sugar molecules in a chain, they cannot be digested by the human body into simple sugars (they are considered “fiber”) and so will not contribute to glycation. They include beta-glucans, such as those found in certain mushrooms and alpha-glucans, such as those in oat and barley bran).]

His protocol includes: 4

1. •Lignans from flaxseed hulls (These are phytoestrogenic fibers known to help control blood sugar and insulin, and also to improve gastrointestinal health, thus enhancing absorption and elimination of foods. They also may improve the effectiveness of mitochondria in energy-generating capacity.);
2. •Amino acids and polypeptides needed as raw material for all enzymatic processes, including the formation of insulin, and anti-aging antioxidants such as glutathione;
3. •Vitamins and minerals and co-factors needed for the body’s antioxidant and cell repair systems;
4. •Dietary fibers (alpha and beta glucans) that help control blood sugar and enhance digestion;
5. •Essential fatty acids;
6. •Anti-glycating supplements: alpha lipoic acid, benfotiamine, and carnosine; and Anti-oxidant supplements: L-carnitine, Ubiquinone (Coenzyme Q10) as discussed below. These can also help with Insulin Resistance (IR).

Alpha lipoic acid (ALA; also known as thiotic acid) is known as a universal antioxidant: 400-times more effective than both vitamins C and E combined, and works equally well in both aqueous and lipid environments. It also recycles vitamins C and E, glutathione, and CoQ10 after they have been oxidized, and is the only antioxidant known to boost cellular levels of glutathione, critical for proper functioning of the immune system. It helps curtail glycation (by preventing the attachment of sugar to proteins), and enhances the transfer of blood sugar into the cells by stimulating glucose uptake. ALA is extensively involved in the Krebs cycle (the mitochondrial process that turns sugar into energy at the cellular level), by neutralizing the free radicals that are normally generated as byproducts of this energy production process. 4 ALA also has the ability to chelate harmful heavy metals such as mercury and lead so that they can be removed from the cells and thus protect them from oxidation by these toxic metals. 6
Benfotiamine, a fat-soluble synthetic variant of vitamin B1, “blocks three of the major bio-chemical pathways through which hyperglycemia does its pro-inflammatory damage, including the formation of AGEs.”4 It also enhances the activity of an enzyme that prevents activation of a “pro-inflammatory compound known as NF-kappa B, and converts harmful blood sugar metabolites into harmless chemicals.” 5
Carnosine, a naturally occurring di-peptide (2 amino acids in the chain), is a powerful antioxidant known to inhibit cross-links between glycated proteins (by chelating excess copper which would otherwise act as a catalyst for glycation and oxidation. It also has the unique ability to repair or remove damaged or ‘misfolded’ proteins, which have been implicated in Alzheimer’s and mad cow. 4
L-Carnitine is formed from the amino acids lysine and methionine, and is responsible for transport of fatty acids from the cellular fluid into the mitochondria, where they can be converted to energy. 10 It has anti-oxidant and membrane-stabilizing effects, and is considered a neuro-protective agent. The acetylized version (Acetyl-L-Carnitine) can cross the blood-brain barrier and is thus important to rejuvenate brain cells. 4
Coenzyme Q10 (CoQ10) is related in structure to vitamins E and K, 11 and works in the mitochondria: to transport electrons during energy production; and to protect them from free radicals formed during normal metabolism. Levels of CoQ10 decline with age. 4

And just to be on the safe side (in case those glycated foods really are harmful), change your cooking methods, especially when it comes to protein sources. Try stewing, steaming and slow-roasting in a low temperature oven, dutch oven, or crock pot. Slow cooking, especially with moisture present, keeps exogenous glycation to a minimum. Avoid fried, seared, and french-fried foods cooked quickly and at high temperatures.
Alpha lipoic acid (ALA; also known as thiotic acid) is known as a universal antioxidant: 400-times more effective than both vitamins C and E combined, and works equally well in both aqueous and lipid environments. It also recycles vitamins C and E, glutathione, and CoQ10 after they have been oxidized, and is the only antioxidant known to boost cellular levels of glutathione, critical for proper functioning of the immune system. It helps curtail glycation (by preventing the attachment of sugar to proteins), and enhances the transfer of blood sugar into the cells by stimulating glucose uptake. ALA is extensively involved in the Krebs cycle (the mitochondrial process that turns sugar into energy at the cellular level), by neutralizing the free radicals that are normally generated as byproducts of this energy production process. 4 ALA also has the ability to chelate harmful heavy metals such as mercury and lead so that they can be removed from the cells and thus protect them from oxidation by these toxic metals. 6
Benfotiamine, a fat-soluble synthetic variant of vitamin B1, “blocks three of the major bio-chemical pathways through which hyperglycemia does its pro-inflammatory damage, including the formation of AGEs.”4 It also enhances the activity of an enzyme that prevents activation of a “pro-inflammatory compound known as NF-kappa B, and converts harmful blood sugar metabolites into harmless chemicals.” 5
Carnosine, a naturally occurring di-peptide (2 amino acids in the chain), is a powerful antioxidant known to inhibit cross-links between glycated proteins (by chelating excess copper which would otherwise act as a catalyst for glycation and oxidation. It also has the unique ability to repair or remove damaged or ‘misfolded’ proteins, which have been implicated in Alzheimer’s and mad cow. 4
1.
2. L-Carnitine is formed from the amino acids lysine and methionine, and is responsible for transport of fatty acids from the cellular fluid into the mitochondria, where they can be converted to energy. 10 It has anti-oxidant and membrane-stabilizing effects, and is considered a neuro-protective agent. The acetylized version (Acetyl-L-Carnitine) can cross the blood-brain barrier and is thus important to rejuvenate brain cells. 4
3.
4. Coenzyme Q10 (CoQ10) is related in structure to vitamins E and K, 11 and works in the mitochondria: to transport electrons during energy production; and to protect them from free radicals formed during normal metabolism. Levels of CoQ10 decline with age. 4

And just to be on the safe side (in case those glycated foods really are harmful), change your cooking methods, especially when it comes to protein sources. Try stewing, steaming and slow-roasting in a low temperature oven, dutch oven, or crock pot. Slow cooking, especially with moisture present, keeps exogenous glycation to a minimum. Avoid fried, seared, and french-fried foods cooked quickly and at high temperatures.
http://web.mac.com/catherinehaug/iWeb/Health-Disease/Glycation.html

MORE ON AGEs

X-Message-Number: 28711
Date: Sun, 3 Dec 2006 12:06:18 -0800 (PST)
From: oberon@vcn.bc.ca
Subject: glycotoxin restriction extends rodent lifespan

[Feed restriction has extended lifespan in a wide variety of short lived
animal species. It had been assumed that the toxic effect of ad-libitum
feed consumption was due to excess calories. In the last several years
this assumption has been proven to be false. In nematodes, the benefit of
feed restriction is now ascribed to the restriction of coenzyme Q. In
drosophila, the benefit of feed restriction has been ascribed to protein
restriction. In mice, the benefit of feed restriction has been ascribed
to glycotoxin restriction. Over the years there have been a number of
failures in CR studies, where lifespan was not extended. These can be
explained, in the case of rodents, by a failure to control for glycotoxin
intake.]

[Glycotoxin content of rodent chow can be increased by roasting it at
high temperatures during sterilization. Rodents are adapted to consuming
only raw food in the wild, and they may be more vulnerable than humans to
the deletarious effects of Advanced Glycation End-products. Below serum
AGE levels closely predicted two year survival. Calorie intake by itself
was without effect. Note that glycotoxins are believed themselves to
affect body weight by influencing water retention.]

Diabetes June 2004 Volume 53 Supplement 2 A343 1426-P
Amelioration of Insulin Resistance, Weight Gain and Markers of Oxidant
Stress in Aging Mice by Dietary Glycotoxin Restriction: A Therapeutic
Alternative to Caloric Restriction?
Insulin Resistance (IR) and T2D are prevalent in older adults, and
preventable in animals by caloric restriction (CR), which is also known
to extend survival. Dietary AGE restriction prevents diabetic tissue
injury and recent data suggest that it may prevent IR in
db/db(+/+) mice. Herein we asked whether AGE restriction and CR have
similar effects on IR and OS in normal mice. In a 24-mo study, body
weight (BW), fasting glucose:insulin ratio (GIR), serum AGE (sAGE),
glutathone (GSH/GSSG), F8-isoprostanes (8-iso) and 2-ear survival were
assessed in C57BL/6 mice (age: 4 mos, n=20/group) kept on
different diets: Group A) regular ad lib (NIH-31, 323 AGE u/mg
protein); Group B) CR (60% of group A (NIA, 329 AGE u/mg); Group C) Low
in AGE, ad lib (NIH-31, L-AGE; 154 AGE u/mg) and Group D) CR (60% of
A) but high in AGE (H-AGE/CR: 928 AGE u/mg). At 24 mos, the following
data were obtained (Table 1):

Table 1
Groups BW fasting- sAGE 8-iso GSH/ 2y-
(g) GIR (u/ml) (pg/ml) GSSG survival
__________________________________________________________
H/CR D 29 11 60 226 90% 0/22
Regular/Ad-Lib A 38 12 42 103 100% 2/22
Regular/CR B 28 21 23 92 160% 5/22
L/Ad-Lib C 31 20 20 58 207% 9/22

Conclusions: 1. Long-term AGE restriction, like CR, prevents
age-related IR, weight gain, systemic OS and extends survival in mice,
but without compromising nutrient or energy content. 2. CR, without
restriction in glycoxidant content reduces BW, but fails to protect
against IR, AGE burden and OS, leading to reduced survival.

[Coenzyme Q10 is nontoxic in nematodes. It is dietary coenzyme Q8 which
reduces their lifespan.]

Science. 2002 Jan 4;295(5552):120-3.
Extension of life-span in Caenorhabditis elegans by a diet lacking
coenzyme Q.
The isoprenylated benzoquinone coenzyme Q is a redox-active lipid
essential for electron transport in aerobic respiration. Here, we show
that withdrawal of coenzyme Q (Q) from the diet of wild-type nematodes
extends adult life-span by approximately 60%. The longevity of clk-1,
daf-2, daf-12, and daf-16 mutants is also extended by a Q-less diet. These
results establish the importance of Q in life-span determination. The
findings suggest that Q and the daf-2 pathway intersect at the
mitochondria and imply that a concerted production coupled with enhanced
scavenging of reactive oxygen species contributes to the substantial
life-span extension.

Mech Ageing Dev. 2006 Jul;127(7):643-6. Epub 2006 Apr 17.
Restriction of amino acids extends lifespan in Drosophila melanogaster.
Dietary restriction extends adult Drosophila melanogaster life span
when the concentration of dietary yeast is diluted in a media with
abundant carbohydrates. Here we vary the concentration of casein as a
source of amino acids in adult diet to uncover a quality of nutrient
yeast responsible for longevity control. Longevity is maximized upon diet
with intermediary levels of casein. Differences in survival are not
caused by elevated age-independent mortality; the longevity maximum at
intermediate casein does not arise because casein is non-specifically
harmful at higher concentrations. Furthermore, fecundity increases when
the level of dietary casein is elevated. The demographic phenotypes of
adult Drosophila maintained on intermediate levels of casein resemble
their response to limited dietary yeast. Dietary restriction through
dilution of yeast may extend longevity because this limits the intake of
amino acids.

[Here's are some examples of failures in a CR experiments.]

Aging (Milano). 1995 Apr;7(2):136-9.
Is late-life caloric restriction beneficial?
Caloric restriction initiated in young mice and rats results in
increases in mean and median life span. When caloric restriction is
implemented in older animals, an increase in life span is still
observed; however, the magnitude of the increase is not as great as that
observed in animals calorie restricted since they were young. Here we
report the results of a pilot study in which caloric restriction was
initiated in mature, older rats. Survival rates and terminal pathology
were characterized and compared between a cohort of 17 continually ad
libitum fed Long Evans rats and a cohort of 18 Long Evans rats, which were
gradually introduced to 33% restriction in diet consumption at 18 months
of age. No difference in the median life span was observed between the
two groups. The data suggest there may be a level of maturity, or a stage
in the aging process, after which caloric restriction no longer increases
longevity.

Exp Gerontol. 1980;15(4):237-58.
Survival and disease patterns in C57BL/6J mice subjected to undernutrition.
Cheney KE, Liu RK, Smith GS, Leung RE, Mickey MR, Walford RL.

[One can avoid excessive AGEs in food by avoiding food that has been
processed at high temperatures. Example: Boiled oatmeal is low in AGEs,
while "Fiber 1" bran cereal is high in AGEs since "Fiber 1" is extruded
at a higher temperature. In general, steam, or boil instead of fry, or
broil. However it must be added that humans are not rodents, and may not
benefit much from dietary AGE reduction.]

[Can one reduce serum AGEs by means other than diet? Yes, activated
carbon can absorb AGEs, and this has increased lifespan in rodents. In
Japan a prescription activated carbon product has been used for years in
the treatment of kidney failure patients. However the primary dietary
toxin specific for humans which is scavenged by this product may have
another source.]

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HOW TO CURE AGES (Kremezin-A is only available in the US as cat medicine)

Kremezin-A orally administered Beaded Activated Carbon which strongly adsorbs Dietary Advanced Glycation Endproducts and Uremic Toxins
Below we present a summary of the major research results for Kremezin (also called AST-120 and Merckmezin), taken from published studies in the scientific peer-reviewed literature. Kremezin is made by the Japanese Kureha Corporationand is currently available for therapeutic use in Japan and Korea for chronic renal failure. It is also available for the same purpose for cats under the name Covalzin. (The Internet archived page for Covalzin as it was sold by Sankyo Lifetech Animal Products is being provided because although that company was sold to Novartis Animal Health in early 2007, Novartis is not yet showing Covalzin among its own products.)
Safety and Interactions
1. "Since AST-120 is not absorbed, it is unlikely that the mechanism of AST-120 antioxidant activity directly participates in radical scavenging in blood; rather, we hypothesize an indirect manifestation of activity, in which substances causing oxidative stress or their precursors are adsorbed in the gastrointestinal tract, thus suppressing their levels in blood."R
2. "Eligible patients were randomly assigned to 1 of 3 doses of AST-120 (0.9, 2.1, or 3.0 g) or placebo 3 times daily for 12 weeks. ... All doses of AST-120 were well tolerated and did not adversely affect the general health status of patients."R
3. "AST-120 is an orally administered adsorbent used in Japan for prolonging time to initiation of hemodialysis and improving uremic symptoms in patients with chronic kidney disease (CKD). As AST-120 is suspected to reduce the progression of CKD by adsorbing renal toxins in the gastrointestinal tract, the objective of the current study was to determine whether binding of AST-120 to creatinine in the intestines could acutely alter creatinine balance, thereby limiting the utility of serum creatinine (sCr) as a measure of progression of renal function. ... Patients with CKD (n = 20) received oral doses of AST-120(3 g t.i.d.) and placebo in a two-way crossover study. Blood and urine were collected for determination of sCr, 24-hour urinary creatinine (UcrV), creatinine clearance (Ccr), and urea nitrogen clearance (URCL). ... Following AST-120 and placebo treatments, ... No significant differences were observed for Ccr and URCL. CONCLUSION: These results indicate that AST-120 has no acute impact on creatinine balance in patients with CKD. Consequently, sCr and other markers of renal function are acceptable measures for assessing changes in renal function following AST-120 treatment."R
Proven and Potential Benefits
1. "The effect of AST-120, an oral adsorbent, on oxidative stress in the systemic circulation in chronic renal failure (CRF) was examined and the potential role of indoxyl sulfate (IS), an uremic toxin adsorbed by AST-120, in inducing the formation of reactive oxygen species (ROS) in the vascular system was studied, in vitro and in vivo [in CRF rats]. ... An increase in the ratio of oxidized to unoxidized albumin was determined ... compared to a control group. The ratio was significantly reduced in the group that received AST-120 of 4 weeks, suggesting that AST-120 inhibits oxidative stress in CRF. ... We propose that AST-120 reduces IS concentrations in the blood that induces ROS production in endothelial cells, thereby inhibiting the subsequent occurrence of oxidative stress in the systemic circulation in renal failure.R
2. "The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various disorders. It is now well established that early glycation products undergo progressive modification over time in vivo to the formation of irreversible cross-links, after which these molecules are termed "AGEs (advanced glycation end products)". AGEs have been implicated in the development of many of the pathological sequelae of diabetes and aging, such as diabetic microangiopathy, ischemic heart disease and neurodegenerative diseases. Recently, digested food-derived AGEs are also found to play an important role in the pathogenesis of AGE-related disorders. Diet is a major environmental source of pro-inflammatory AGEs. Indeed, restriction of dietary glycotoxins decreases excessive AGE levels and subsequently reduces the inflammatory responses in patients with diabetes. These observations suggest that inhibition of absorption of dietary AGEs may be a novel target for therapeutic intervention in the above-mentioned AGE-related disorders. AST-120 (Kremezin(R)) is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) by removing uremic toxins. We have recently found that AST-120 binds to carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs in vitro and that administration of AST-120 decreases serum levels of AGEs in non-diabetic CRF patients. These findings suggest that digested food-derived AGEs such as CML may be a novel molecular target for oral adsorbent AST-120 and that AST-120 could exert beneficial effects on CRF patients by adsorbing diet-derived AGEs and subsequently decreasing serum AGE levels. If our speculation is correct, AST-120 may have therapeutic potentials for the treatment of patients with various AGE-related disorders as well. In this paper, we would like to propose the possible ways of testing our hypotheses. Does the long-term treatment of AST-120 decrease serum and tissue levels of AGEs in diabetic patients? Does this treatment also reduce the risk for the development and progression of diabetic vascular complications such as diabetic retinopathy or ischemic heart disease? If the answers are yes, do the serum and/or tissue levels of AGEs after AST-120 treatment predict its beneficial effects on diabetic vascular complications? How about the effects of AST-120 on Alzheimer's disease, another AGE-related neurodegenerative disorder? Does the treatment of AST-120 reduce the risk for Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? These prospective studies will provide further valuable information whether the inhibition of absorption of dietary AGEs by AST-120 could be clinically relevant."R
3. "Indoxyl sulfate shows nephrotoxicity and is a stimulating factor for progression of chronic kidney disease (CKD). ... [In rats] Administration of Kremezin significantly decreased serum and urine levels of indoxyl sulfate and serum creatinine and significantly increased creatinine clearance as compared with control values. The change in serum indoxyl sulfate noted from the initial to the final week showed a positive correlation with the change in serum creatinine and a negative correlation with the change in creatinine clearance. Kremezin significantly reduced urine levels of acrolein, a marker of oxidative stress, as compared with control levels. CONCLUSIONS: The indoxyl sulfate-lowering capacity of oral adsorbents affects the prognosis of kidney function in CKD. The more serum indoxyl sulfate is reduced, the better kidney function is preserved. Kremezin alleviates oxidative stress in the kidneys by reducing serum levels of indoxyl sulfate."R
4. "We previously reported a significant increase in plasma TGF-beta1 in patients with chronic renal failure (CRF). Progression of CRF may be caused by persistent renal production of TGF-beta1. In CRF rat models, an oral carbonic absorbent (AST-120) reduces the expression of the TGF-beta1 gene in the kidney, and delays the progression of CRF, in part by alleviating the overload of indoxyl sulfate. The aim of this study was to evaluate the effect of AST-120 on plasma levels of indoxyl sulfate and TGF-beta1 in CRF patients. METHODS: Ten CRF patients (aged 59.3 +/- 9.5 years, 5 men, serum creatinine 4.37 +/- 1.72 mg/dl) were enrolled in this study. All patients maintained a regular dietary therapy and the same medication throughout the study. AST-120 was added at a dose of 6 g/day. ... Administration of AST-120 significantly reduced the plasma levels of indoxyl sulfate (1.42 +/- 1.50 vs. 1.26 +/- 1.40 mg/dl, P < 0.05) and TGF-beta1 (17.9 +/- 7.2 vs. 10.6 +/- 4.7 ng/ml, P < 0.05) and improved the slope of the reciprocal of serum creatinine (-0.061 +/- 0.041 vs. -0.032 +/- 0.055 dl/mg/year, P < 0.05). CONCLUSIONS: These results support the notion that indoxyl sulfate and TGF-beta1 may be involved in the progression of CRF, and that the oral adsorbent AST-120 may suppress the progression, at least in part, by reducing overproduction of TGF-beta1."R
5. "We studied whether adding the spherical adsorptive carbon AST-120 to conventional treatments is effective in inhibiting progression of chronic kidney disease (CKD) at the stage of moderate decrease in renal function. METHODS: 43 CKD patients with moderately impaired renal function indicated by glomerular filtration rate (GFR) of 20-70 ml/min ... were enrolled in the study. 26 patients showing a decrease of GFR by 5 ml/min during a 1-year observation period were randomized to receive ongoing treatments only (control group, 12 cases) or with AST-120 co-administered with ongoing treatment (AST-120 group, 14 cases). The intervention period was 1 year and the change in GFR was the primary evaluation variable. RESULTS: ... the rate of decline in GFR was significantly retarded (p < 0.001) in the AST-120 group while no significant difference was observed in the control group. CONCLUSION: These results suggest that co-administration of AST-120 with conventional treatments retards decline in renal function in CKD patients with moderate decrease in renal function."R
6. "Advanced glycation end products (AGEs) are senescent macroprotein derivatives that are formed at an accelerated rate in patients with chronic renal failure (CRF). AGE formation and accumulation in plasma and vascular tissues contribute to accelerated atherosclerosis in this devastating disorder. AST-120 is an oral adsorbent that attenuates the progression of CRF by removing uremic toxins. Recently, AST-120 has been reported to reduce the progression of atherosclerosis as well. However, whether AST-120 decreases serum levels of AGEs and subsequently exerts atheroprotective properties remains to be elucidated. Ten nondiabetic CRF patients were enrolled in this study. All patients were kept on regular therapeutic diet and medications throughout the study. Serum AGE levels before and after AST-120 treatments were measured using enzyme-linked immunosorbent assay. ... Administration of AST-120 (6 g/day) for 3 months significantly decreased serum levels of AGEs in nondiabetic CRF patients, whereas AGE levels remained unchanged in age- and renal function-matched CRF patients without AST-120 treatment (n = 6). Patient serum after AST-120 treatment significantly reduced mRNA levels of receptor for AGEs, monocyte chemoattractant protein-1, and vascular adhesion molecule-1 in HUVECs [cultured human umbilical vein endothelial cells] compared with serum before treatment. Moreover, in vitro, AST-120 was found to adsorb carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs. This study suggests that atheroprotective properties of AST-120 can be ascribed, at least in part, to its AGE-lowering ability via absorption of CML."R
7. "Using a rat model ... focusing on indoxyl sulphate (IS) as a representative UTx [uraemic toxin], we analysed the effect of an oral charcoal adsorbent AST-120, which removes uraemic toxins and their precursors from the gastrointestinal tract, on bone turnover. ... In rats treated with vehicle, serum IS level increased with time after renal dysfunction, while bone formation decreased accompanied by down-regulation of the parathyroid/parathyroid-related peptide hormone receptor, alkaline phosphatase and osteocalcin genes. Administration of AST-120 inhibited the accumulation of IS in blood and ameliorated bone formation. Bone formation rate was 2.4 +/- 1.7 microm(3)/m(2)/year in controls given vehicle and was 11.7 +/- 2.4 microm(3)/m(2)/year in rats administered with AST-120 (P < 0.05). AST-120 treatment also reversed the down-regulation of osteoblast-related genes. ... Administration of the oral charcoal adsorbent AST-120 decreases the osteoblast cytotoxicity of UTx including IS, and suppresses progression of low bone turnover in uraemic rats."R
8. "A novel charcoal compound, AST-120, has been used for over a decade in Japan to prevent progression of CKD. It is thought that the oral administration of AST-120 blocks the intestinal absorption of tryptophan-derived indole. This prevents the hepatic conversion of indole to indoxyl sulfate (IS). IS has been shown to stimulate the production of profibrotic cytokines such as transforming growth factor-beta. AST-120 lowers IS in a dose dependent fashion and does not change the creatinine appearance rate in the urine."R
9. "Kremezin was given to 48 enrolled undialyzed patients with a median Scr [serum creatinine} level of 4.3 mg/dL. Rates of decline of 1/Scr, as well as the time for Scr level to reach 10 mg/dL, the critical value requiring dialysis, were compared before and after administration of Kremezin. RESULTS: During the 2-year therapeutic period, 1/Scr gradients were significantly attenuated (P = 0.0083), and the estimated time to dialysis was prolonged from 16.3 +/- 16.3 months to 29.8 +/- 24.1 months (P = 0.002). When the patients were divided into two groups, based on of systolic blood pressure (SBP), defined by the World Health Organization (WHO) classification, a significantly smaller number of patients in the low blood pressure group (SBP < 160 mmHg) were introduced to dialysis (P = 0.0005), and the estimated time to dialysis was significantly extended in the low blood pressure group (P = 0.0125). CONCLUSION: In addition to the control of blood pressure in undialyzed patients, Kremezin has additive salutary effects to halt the progressive loss of renal function, resulting in the delay of dialysis."R
10. "Intima media thickness (IMT) and stiffness of the carotid arteries is related to coronary artery disease, and chronic renal failure patients are at high risk for such diseases. ... The aim of the present study was to determine whether AST-120 affects carotid artery IMT and pulse wave velocity (PWV) in patients with chronic renal failure not undergoing dialysis. METHODS: Fifty patients with non-diabetic chronic renal failure were randomly divided into two groups: 30 patients (18 men and 12 women; mean age 53.5 years; mean serum creatinine 3.2 mg/dl) who were given AST-120 (6.0 g/day) and 20 patients (12 men and 8 women; mean age 52.0 years; mean serum creatinine 3.5 mg/dl) who were not given AST-120. Thirty healthy age-matched subjects (18 men and 12 women; mean age 51.5 years; mean serum creatinine 0.9 mg/dl) were also included. The treatment period was 24 months. IMT and arterial stiffness were measured before and after treatment. RESULTS: The slope of the reciprocal serum creatinine concentration over time became significantly less steep in the AST-120 group than in the non-AST-120 group (p < 0.001). Before treatment, carotid artery IMT differed little between the AST-120 group (0.90 +/- 0.22 mm) and the non-AST-120 group (0.88 +/- 0.20 mm). IMT in these two groups was significantly greater than IMT in the control group (0.64 +/- 0.14 mm) (p < 0.01). Carotid IMT in the AST-120 group decreased slightly but not significantly to 0.84 +/- 0.20 mm after 12 months and then significantly after 24 months to 0.78 +/- 0.18 mm (p < 0.05). Carotid IMT in the non-AST group showed little change throughout the experimental period. PWV differed little between the AST-120 group (1,980 +/- 330 cm/s) and the non-AST group (1,940 +/- 360 cm/s) before treatment. PWV values in these two groups were significantly greater than PWV in the control group (1,280 +/- 240 cm/s) (p < 0.01). After 12 and 24 months, PWV in the AST-120 group decreased significantly to 1,840 +/- 280 cm/s (p < 0.05) and to 1,780 +/- 260 cm/s (p < 0.05), respectively; however, PWV in the non-AST group showed a slight increase during the experimental period. CONCLUSION: The data suggest that AST-120 may reduce arterial stiffness and IMT in non-diabetic chronic renal failure patients before dialysis."R
11. "Tryptophan (TRP), an essential amino acid, is bound mostly to albumin in plasma. However, it is reported that binding is inhibited by indoles that accumulate in uremic plasma. This may be responsible for the malnutrition observed in uremic patients. AST-120, an oral adsorbent of uremic toxins, can reduce concentrations of indoxyl sulfate (IS), the most abundant indolic metabolite in uremic plasma. We therefore investigated whether AST-120 recovers TRP binding to plasma proteins and improves the nutritional state of uremic patients. METHODS: The in vitro binding ratio of TRP to bovine serum albumin (BSA) was measured in the presence of IS by the equilibrium dialysis technique. In addition, five predialysis patients with chronic renal failure (CRF) were administered AST-120 for 2 months. Plasma concentrations of total TRP, IS, and free TRP were measured in five healthy volunteers (normal [N] group) and five patients with CRF before and after 2 weeks of AST-120 therapy (6 g/d). Their nutritional statuses also were compared before and after 2 months of AST-120 administration. RESULTS: IS inhibited in vitro binding of TRP to BSA in a dose-dependent manner. Total TRP concentrations and protein-binding ratios in patients with CRF (0.90 +/- 0.08 mg/dL and 68.7% +/- 6.8%, respectively) were significantly lower than those in the N group (2.45 +/- 0.45 mg/dL and 92.0% +/- 1.4%, respectively). However, a 2-week administration of AST-120 significantly reduced IS levels from 1.79 +/- 1.01 to 1.15 +/- 0.85 mg/dL (N group, 0.06 +/- 0.01 mg/dL), increased total TRP levels (1.16 +/- 0.18 mg/dL), and improved the TRP plasma protein-binding ratio to 83.1% +/- 3.8%, whereas total protein and albumin levels remained unchanged. After 2 months of AST-120 administration, serum albumin and transferrin levels increased significantly. CONCLUSION: AST-120 improves nutritional state, at least partly through correcting impaired TRP metabolism, in patients with CRF."R
12. "AST-120 significantly reduced renal expression of intercellular adhesion molecule (ICAM)-1, osteopontin, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-beta1, as well as clusterin. ... AST-120 also decreased serum and urinary levels of indoxyl sulfate and the overload of indoxyl sulfate in tubular cells. CONCLUSIONS: AST-120 ameliorates tubulointerstitial injury by reducing renal expression of ICAM-1, osteopontin, MCP-1, TGF-beta1 and clusterin in 1/2NxOLETF rats."R
13. The relationship between insulin resistance and local uremic toxins was examined using an oral adsorbent. Fourteen rats demonstrating a diabetic state underwent two-thirds, nephrectomy and were divided into two groups. The control group was fed standard rat chow, and the test group was fed standard rat chow containing 5% AST-120. The target level of blood glucose was achieved by controlling the dosage of exogenous insulin. All rats were sacrificed at week 6. Body weight, blood glucose level, and renal function at week 6 were not significantly different between both groups. However, the mean blood glucose level and the mean dose of exogenous insulin in the AST-120-fed group were significantly reduced as compared with the control group. The results of the present study indicate that administration of an oral adsorbent in diabetic nephropathy decreases the doses of exogenous insulin and improves insulin resistance, and that uremic toxins which exist in the gastrointestinal tract play important roles."R
14. "We have reported that oral sorbent AST-120 (AST) is effective in delaying the induction of dialysis in patients with chronic renal failure (CRF) because of its effect on lipid metabolism. To clarify the precise mechanism of AST in lipid abnormalities in CRF, we examined the effect of AST on plasma lipid profile, total bile acids (TBA), and lipoprotein lipase (LPL) activity in experimental uremic rats. METHODS: Uremic rats were prepared using male Wistar rats by ligating 5/6 of the renal artery. Uremic rats were randomly divided into two groups as follows: a control group in which rats were maintained on the standard diet and an AST group in which rats were maintained on a diet containing 5 g of AST per 100 g of standard diet for 10 weeks. Plasma LPL activity was measured as free fatty acid (FFA) generation after intravenous administration of heparin. RESULTS: Plasma creatinine at 1.5 +/- 0.1 mg/dl was lower in the AST group than the 1.9 +/- 0.5 mg/ml level in the control group. AST significantly decreased plasma total cholesterol from 192 +/- 29 to 142 +/- 25 mg/dl, triglycerides from 198 +/- 71 to 99 +/- 38 mg/dl, and TBA from 19.6 +/- 2.6 mumol/liter to 8.8 +/- 3.5 mumol/ml. Plasma LPL activity at 0.22 +/- 0.01 mumol FFA/min/hr was significantly higher in the AST group than 0.15 +/- 0.03 mumol FFA/min/hr in the control group. CONCLUSIONS: These results suggest that AST may improve plasma lipid abnormalities by binding to bile acids in the intestinal lumen and preventing their reabsorption and inhibiting the reduction of LPL activity in experimental uremic rats."R
http://morelife.org/supplements/kremezin.html

The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various disorders. It is now well established that early glycation products undergo progressive modification over time in vivo to the formation of irreversible cross-links, after which these molecules are termed "AGEs (advanced glycation end products)". AGEs have been implicated in the development of many of the pathological sequelae of diabetes and aging, such as diabetic microangiopathy, ischemic heart disease and neurodegenerative diseases. Recently, digested food-derived AGEs are also found to play an important role in the pathogenesis of AGE-related disorders. Diet is a major environmental source of pro-inflammatory AGEs. Indeed, restriction of dietary glycotoxins decreases excessive AGE levels and subsequently reduces the inflammatory responses in patients with diabetes. These observations suggest that inhibition of absorption of dietary AGEs may be a novel target for therapeutic intervention in the above-mentioned AGE-related disorders. AST-120 (Kremezin) is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) by removing uremic toxins. We have recently found that AST-120 binds to carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs in vitro and that administration of AST-120 decreases serum levels of AGEs in non-diabetic CRF patients. These findings suggest that digested food-derived AGEs such as CML may be a novel molecular target for oral adsorbent AST-120 and that AST-120 could exert beneficial effects on CRF patients by adsorbing diet-derived AGEs and subsequently decreasing serum AGE levels. If our speculation is correct, AST-120 may have therapeutic potentials for the treatment of patients with various AGE-related disorders as well. In this paper, we would like to propose the possible ways of testing our hypotheses. Does the long-term treatment of AST-120 decrease serum and tissue levels of AGEs in diabetic patients? Does this treatment also reduce the risk for the development and progression of diabetic vascular complications such as diabetic retinopathy or ischemic heart disease? If the answers are yes, do the serum and/or tissue levels of AGEs after AST-120 treatment predict its beneficial effects on diabetic vascular complications? How about the effects of AST-120 on Alzheimer's disease, another AGE-related neurodegenerative disorder? Does the treatment of AST-120 reduce the risk for Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? These prospective studies will provide further valuable information whether the inhibition of absorption of dietary AGEs by AST-120 could be clinically relevant.
http://www.biomedexperts.com/Abstract.bme/17331665/Oral_administration_of_AST-120_Kremezin_is_a_promising_therapeutic_strategy_for_advanced_glycation_end_product_AGE_-r

http://www.cureendometriosis.com/the-scary-link-between-endometriosis-and-dioxin-be-sure-to-avoid-it/

"Except for phytoestrogens, most of the tested chemicals (DDT and its metabolites, aldrin, alpha- and beta-endosulfan, toxaphen, trans-nonachlor) show higher affinities for hPR than for hERalpha, indicating that the interaction with the progesterone receptor could contribute to the endocrine-disrupting effects imputed to these chemicals."
https://www.mims.com/Page.aspx?menuid=pubmeddetail&pmid=medline10n0494\14579009.xml&h=Fungicide

Berberine reduces insulin resistance: The roles for glucocorticoid receptor and aryl hydrocarbon receptor
To the Editor:
We read with interest an article by Zhao et al. entitled “Berberine reduces insulin resistance induced by dexamethasone in theca cells in vitro” recently published in Fertility and Sterility (1). The authors showed that synthetic glucocorticoid dexamethasone-induced insulin resistance in theca cells is diminished by berberine.
The uterus is a muscle. Like all muscles, it can contract and relax. During your period, it contracts more strongly. Sometimes when it contracts you feel a cramping pain.
The uterine muscles contract whenprostaglandins are produced. Prostaglandins are chemicals made by the lining of the uterus. Before your period, the level of these chemicals increases. At the start of your period, prostaglandin levels are high. As you menstruate, the level of prostaglandins decreases. This is why pain tends to lessen after the first few days of the period
Medications
Certain medications, called NSAIDs (non-steroidal anti-inflammatory drugs), block the body from making prostaglandins. This makes cramps less severe. These drugs also can prevent some symptoms, such as nausea and diarrhea. Most NSAIDs, such as ibuprofen and naproxen, can be bought over-the-counter (without a prescription). Another type, COX-2 inhibitors, may be prescribed.
NSAIDs work best if taken at the first sign of your period or pain. You usually take them for only 1 or 2 days and should avoid alcohol during this time. Women with bleeding disorders, liver damage, stomach disorders, or ulcers should not take NSAIDs.
Hormonal Contraception
Hormonal contraception, such as birth control pills, patches, and vaginal rings, also reduce menstrual pain. In some cases, the hormonal intrauterine device (IUD) may be recommended. The hormones in these types of contraception help control the growth of the lining of the uterus so less prostaglandin is made. That means there are fewer contractions, less blood flow, and less pain. Hormones may stop the growth of fibroids and endometriosis. However, they often grow back when treatment stops. If needed, contraception can be used with other medications that decrease estrogen levels or stop menstrual cycles. This helps prevent pain before it starts.
http://www.acog.org/publications/patient_education/bp046.cfm