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Telomere length associated with PCOS finds new research

The length of the telomeres on leukocytes has been found to be associated with polycystic ovarian syndrome (PCOS) for the first time, according to a study published in the current issue of the Journal of Clinical Endocrinology and Metabolism, on Dec. 3, 2013

Telomeres are specialized chromatin structures located at the ends of eukaryotic chromosomes.  They serve to protect our genes from the damage caused as they age and are often compared to the plastic caps at the ends of shoelaces, as their purpose is the same: to stop damage or fraying occurring.  Every time a cell divides, the telomere at the end of its chromosome shortens.  The amount by which it shortens each time varies greatly between different people and within the context of different lifestyle practices such as dietary habits, stress management and exercise.

Telomere length plays a clear role in many disease processes and is linked to the speed at which ageing occurs in the body.  The longer your telomeres, the slower your cells, and thus you, age.

The research team from Fudan University in Shanghai, China hypothesized that leukocyte telomere length or LTL played an important role in the pathophysiology, or disordered metabolic and endocrine processes, that form PCOS.  The scientists used a polymerase chain reaction or PCR technique to measure the length of the telomeres in women with PCOS and those without who served as controls for the study.  When the results were analyzed and adjusted for the age of the women, the researchers found that women with PCOS had significantly shorter LTLs than women without PCOS.

The mean telomere length in PCOS patients was comparable to women in the control group who were over 6 years older, on average.  The women who had the shortest telomere length had a significantly higher risk of disease than those with the longest telomeres, after adjusting for age.  Women in the bottom two-thirds of the group for telomere length had a 60% greater risk of disease than the third of the group who had the longest telomeres.

The researchers concluded that “We provide the first report that LTL is strongly associated with PCOS. This study suggests a new role for LTL in the pathophysiology of PCOS and might have important implications for our understanding of the etiology of the disease.”

PCOS affects about 10 percent of women, though some estimates put that figure as high as 25 percent depending upon the demographic. PCOS is the leading cause of female infertility and the disease greatly increases the risk of premature cardiovascular disease including heart attack and stroke.  The condition appears to be more prevalent in lesbian women than in heterosexual women, though it is not known why this is. Polycystic ovarian syndrome is characterized by excess levels of male hormones which are triggered by excess levels of insulin which act upon the theca cells of the ovaries stimulating them to produce testosterone, irregular ovulation and menstruation which can lead to infertility and is associated with an increased risk for insulin resistance, which can lead to diabetes and heart disease.

More Information:Although this research may not initially be particularly uplifting for women with PCOS, it is important to note that telomere length can be influenced by a healthy lifestyle, including regular exercise, a healthy diet and stress reduction techniques, all of which are proven to improve PCOS outcomes.  Research published in journals such as the Lancet, PLoS One and Menopause over the last two years have consistently found improvements in telomere length with interventions including a regular exercise program, a Mediterranean diet, a plant-based diet and stress reduction practices such as meditation and yoga.

Li Q, Du J, Feng R, Xu Y, Wang H, Sang Q, Xing Q, Zhao X, Jin L, He L…. (2013) A possible new mechanism in the pathophysiology of polycystic ovary syndrome: The discovery that leukocyte telomere length is strongly associated with PCOS. The Journal of clinical endocrinology and metabolism. PMID: 24302747

Boccardi V, Esposito A, Rizzo MR, Marfella R, Barbieri M, & Paolisso G. (2013)Mediterranean diet, telomere maintenance and health status among elderly. PloS one, 8(4). PMID: 23646142

Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJ, Daubenmier J…. (2013) Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. The Lancet Oncology, 14(11), 1112-20. PMID: 24051140

Kim JH, Ko JH, Lee DC, Lim I, & Bang H. (2012) Habitual physical exercise has beneficial effects on telomere length in postmenopausal women. Menopause (New York, N.Y.), 19(10), 1109-15. PMID: 22668817

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Placentas of women with PCOS are twice as likely to be defective

A new study published on June 11, 2013 has found for the first time that the placentas of women with PCOS are at least twice as likely to be defective in several different respects when compared with the placentas of healthy women.

The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered.

Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS.

Women with PCOS were 2.8 times more likely to have placental alterations of some form with 73% of women with PCOS had placentas with some degree of abnormality, not including size, weight or thickness, compared to only 42% of healthy women in the control group.

Researchers from the Obstetrics and Gynaecology Unit of the University of Modena and Reggio Emilia in Italy examined the placentas of 30 women with polycystic ovarian syndrome and 60 women who had neither a diagnosis of PCOS nor any of the features of PCOS to determine whether there was any difference in the structure of the placenta between the two groups.  All women were enrolled in the study at the very beginning of their pregnancies, prior to the seventh week of pregnancy, or around 3 weeks from the first missed period.  Blood tests, ultrasounds and clinical and obstetric examination data were collected at the beginning of the study and throughout the pregnancies.  Once the women had delivered their babies, the placenta was examined by a pathologist and under a microscope.

To reduce the chance that the results may be affected by factors such as obesity or the effects of fertility drugs, only women with PCOS who had a body mass index (BMI) of less than 30 kg/m2 and who had conceived naturally, without the aid of ovulation induction drugs or other methods of assisted reproduction and who were experiencing an uncomplicated pregnancy were included in the study.

The researchers, led by Stefano Palomba, found that women with PCOS did indeed tend to have more abnormalities in their placentas than women without the condition, which may contribute towards explaining the higher rate of pregnancy complications that women with PCOS encounter compared to the general population.

The size of the placenta, as measured by weight, volume and thickness, were “significantly inferior” in women with PCOS and they were more likely to have an irregular shape and a greater number of coils in the umbilical cord.  The average umbilical cord has one coil every five centimetres.  Cords which coil significantly more or less than this, tend to be associated with a higher incidence of moderate or severe decreases in foetal heart rate.

The majority of pregnancy complications are due to two things: problems with the way the placenta is growing or the way it is attaching to the uterine wall, or defects in the cells called trophoblasts that encapsulate the embryo when it is very young and which supply nutrients to it before the placenta develops.  Trophoblasts also form a large part of the placenta later on.

Women with PCOS have been observed to have alterations in endovascular trophoblast invasion or the connection of the baby’s blood supply to the blood supply of the mother’s uterus.  This is related to the insulin resistance and high levels of androgens present in women with PCOS.

Under the microscope, differences were also noted in the extent of villous and intervillous spaces, the extent of fibrosis, endovascular trophoblast depth, extension and structure, mitotic activity or the rate at which the cells were growing and dividing.  Women with PCOS averaged 3.5 ‘placental lesions’ versus only 1.4 in the control group.

Whilst no research has, to date, been performed on the effect that d-chiro inositol may have on the health of a placenta, it is reasonable to assume that the significant reductions in insulin resistance and androgen production that it causes in women with PCOS would be very likely to have a positive effect on the growing placenta.

More information:

Palomba, S. (2013-06-11) Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome. . DOI: 10.1093/humrep/det250  PMID: 23756703

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RU-58841 or PSK-3841 – might it help PCOS hair loss?

RU58841A reader recently mentioned coming across this drug which was first studied in the 1990′s for the treatment of male pattern baldness, or androgenetic alopecia in men.  It is now known as PSK-3841 and has also formerly been known as HMR-3841.

A 1997 study of nude mice with skin transplants from balding male scalps found that those mice treated with the drug had four times the number of hair follicles regrow hair in the second cycle after implantation.  It was a small study, only 20 mice, 10 of which were controls, and four times the number of hair follicles equates to 8 out of 29 as opposed to 2 out of 28.

Interest in the drug for the treatment of hair loss dwindled, perhaps due more to commercial potential and chemical stability reasons than efficacy as the later studies of RU58841 have focused on different chemical forms of the drug and combining it with various nanoparticles to enhance delivery.  Recent years have seen the odd study pop up in relation to RU58841 and the treatment of acne and prostate cancer, which are conditions also driven by testosterone, however, the most recent study published in relation to RU58841 was back in 2008.

RU58841 is a non-steroidal anti-androgen drug, which competes with dihydrotestosterone or DHT for binding at the receptors where it causes hirsutism or hair loss.  It has been evaluated as being approximately equivalent in strength to hydroxyflutamide, a drug which is sometimes used in PCOS to treat hirsutism or androgenetic alopecia.  One study in 1998 concluded

“The potency of RU58841 was comparable to that of hydroxyflutamide. From this result, topical application of RU58841, which is considered to be a potential therapy for skin diseases, may induce systemic side effects. However, RU58841, on topical application, revealed a potent increase in density, thickening, and length of hair in the macaque model of androgenetic alopecia, whereas no systemic effects were detected. Together our results suggest that RU58841 may have potent antagonism to the wt AR (wild type androgen receptor) and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, androgenetic alopecia, and hirsutism.”

When compared with the antiandrogenic compound cyproterone acetate, PSK-3841 exhibited a 20% increase in androgen receptor binding. The compound binds to both the ligand and regulatory domains of the androgen receptor.  PSK-3841 exerts allosteric binding effects and may provide a unique mechanism of action in the treatment of alopecia.

Studies to date have been limited to animal studies and in vitro studies or studies performed on cultured cell lines in petri dishes.  For this reason, a great deal of caution should be exercised when considering RU58841.  Neither short-term nor long-term safety data is available for the use of RU58841 in humans, although the information to date indicates that the action of the drug should be localised to the skin where it is applied.

A likely benefit of RU58841 for men in comparison to the arsenal of anti-androgenic drugs already available on the market, is the purported lack of a systemic effect.  For men, many anti-androgenic drugs reduce systemic testosterone levels resulting in testosterone deficiency symptoms such as reduced sexual desire and ability to achieve and maintain an erection, reduced ejaculate volume, lethargy and fatigue, reduced muscle mass, increased body fat, reduced bone mass and increased risk for osteoporosis, breast development and depression.

For women with PCOS, however, a decrease in systemic testosterone levels would generally be beneficial as testosterone does not only affect the androgen receptors in the skin and scalp.  One possible scenario where a non-systemic anti-androgenic action might be desirable may be in when a woman is pregnant and carrying a male foetus, as taking anti-androgenic drugs whilst pregnant can lead to serious consequences for a developing male foetus.

RU58841 appears to be available for purchase through several outlets, including a company called Kane, however, it is horrifically expensive at around $225 for 10 grams, a supply which is likely to last for just 100 applications and I doubt the legality of selling a drug which has not passed any human safety or efficacy testing.

A forum called Bald Truth Talk has quite extensive instructions for making the raw drug up into a solution which is suitable for topical application.  These instructions imply that the product has a very limited shelf-life once made up into solution using alcohol and propylene glycol and that it is necessary to make up a fresh batch every 2-3 days, but preferably every day.

A company called Proskelia Pharmaceuticals which are a part of ProStrakan Pharmaceuticals apparently completed Phase I and Phase II clinical trials of the drug after purchasing it and changing its name to PSK 3841.  They used  studies applied the drug in a solution made with 70% alcohol in 2002 and 2003, however, the results of those studies have not been published, nor has any apparent progress been made towards bringing the drug to market.

A 2005 review article summarised the research into PSK 3841 thus:

“A topical, non-steroidal androgen antagonist, PSK-3841 (formerly HMR-3841 and RU-58841), is being investigated in France by Proskelia for possible therapeutic value in AGA and acne. The compound was is Phase II clinical trials as of January 2004, and was originally researched by Roussel-Uclaf and Hoechst Marion Roussel. When compared with the antiandrogenic compound cyproterone acetate, PSK-3841 exhibited a 20% increase in AR binding. This compound binds to both the ligand and regulatory domains of the androgen receptor. PSK-3841 exerts allosteric binding effects and may provide a unique mechanism of action in the treatment of alopecia.

Imamura et al. noted that this compound prevents androgenetic follicular regression in bald stumptailed macaques; however, it does not promote follicular cell growth directly. Photographic and folliculogram evaluations of combined PSK-3841 5% plus minoxidil 2%, or minoxidil 5% versus previous results from each compound’s performance alone were compared. The most rapid hair regrowth in 1 month was observed in the PSK-3841 5% plus minoxidil 5% group, followed by 2 months for the PSK-3841 5% plus minoxidil 2% group. At 3 months, hair regrowth was comparable for both PSK-3841 5% and minoxidil 5% alone. At the 3-month interval, the researchers noted that both combined groups had regrowth of long-terminal hairs that persisted for 6 – 12 months. The combined groups also boasted greater anagen conversion and follicular enlargement over the individual compounds alone. It was concluded that the combined treatment groups experienced the greatest impact early on; however, after 1 year had elapsed, no difference was observed in the combined treatment groups versus PSK-3841 or minoxidil used alone.

Pan et al. compared the antiandrogen effects of RU-58841 with other known antiantrogens, hydroxyflutamide, Casodex™ (bicalutamide) and genisten in human prostate cells. PSK-3841 demonstrated suppression of DHT activation of the androgen receptor competitively, and in a dose-dependent manner similar to the other antiandrogens. Pan et al. applied topical RU-58851 5% to the bald scalp of stumptailed macaques. Researchers evaluated folliculogram results and noted an increase in the number of anagen follicles and a decrease in telogen follicles as compared with baseline. The PSK-3841-treated group displayed progression from telogen to anagen and an increase in follicle size as opposed to the control group. No systemic side effects were reported. PSK-3841, dosed at 100-fold the therapeutic tested range, showed no signs of systemic antiandrogenic effects. Pan et al. described results from RU-58841 as inducing “remarkable effects on hair and folliclar regrowth in the bald frontal scalp of macaques.”

Brouwer et al. studied the effects of PSK-3841 (1%) in human scalp grafts on testosterone-conditioned nude mice. The PSK-3841-treated grafts were compared with controltreated grafts. The PSK-3841 grafts showed increased recycling. A second hair cycle was noted in 28% of the active follicles of the PSK-3841 grafts versus 7% in the placebo-treated group. PSK-3841 treated mice also had greater linear hair growth rates (LHGR). However, PSK-3841 had no effect on hair diameter.

Battmann et al. investigated PSK-3841 in the intact hamster model in which the flank organ area is evaluated; this organ consists mainly of androgen-dependent sebaceous tissue. PSK-3841 1 – 100 ?g/animal resulted in both a dose- and time-related reduction in flank organ area. No effects on T levels were noted at this dose range or mode of delivery. In contrast, the androgen-dependent sebaceous tissue of the flank organ area of the controltreated hamsters increased. When PSK-3841 was administered via the subcutaneous route, the higher doses of 300 and 1000 ?g/animal were required to yield the antiandrogen effects. Battmann et al. also tested PSK-3841 via percutaneous, subcutaneous and oral routes of administration in the rat model. Results reported that systemic antiandrogenic effects were only seen at the highest titrated dose of 10 mg. Results from the previously described experiments led researchers to conclude that PSK-3841 is a ‘potent local antiandrogen’ with a favourable safety margin.”

It is difficult to remain patient waiting for new drugs to be developed and properly tested and brought to market, however, there is significant risk of unknown side-effects in taking matters into your own hands with an unapproved drug which has not been properly tested on humans.

More Information:

Battmann T, Bonfils A, Branche C, Humbert J, Goubet F, Teutsch G, & Philibert D. (1994)RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism. The Journal of steroid biochemistry and molecular biology, 48(1), 55-60. PMID: 8136306

De Brouwer B, Tételin C, Leroy T, Bonfils A, & Van Neste D. (1997) A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice. The British Journal of Dermatology, 137(5), 699-702. PMID: 9415227

Imamura, K. (1998-03–1) The effect of topical RU58841 (androgen receptor blocker) combined with minoxidil on hair growth in macaque androgenetic alopecia. , S207. DOI: 10.1016/S0923-1811(98)84240-0

Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis ChC, Blume-Peytavi U…. (2005) RU 58841-myristate–prodrug development for topical treatment of acne and androgenetic alopecia. Die Pharmazie, 60(1), 8-12. PMID: 15700772

Pan HJ, Wilding G, Uno H, Inui S, Goldsmith L, Messing E, & Chang C. (1998) Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques. Endocrine, 9(1), 39-43. PMID: 9798729

Poulos, Georgann A. (2005-02–1) Investigational medications in the treatment of alopecia. , 14(2), 177-184. DOI: 10.1517/13543784.14.2.177

ISRCTN49873657 – A double blind, randomised, vehicle-controlled, safety and tolerance study of topical PSK 3841 solution at 5% administered twice daily over four weeks to healthy Caucasian males with androgenetic alopecia

ISRCTN71083772 – A multi-centre, double-blind, randomised, vehicle-controlled study for a quantitative estimation of hair re-growth in male subjects with androgenetic alopecia treated over 6 month with two ethanolic PSK 3841 solutions (2.5% and 5%)

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New study recommends d-chiro inositol and myo-inositol as first line treatment for PCOS

Buy DCI D-Chiro Inositol for PCOS polycystic ovarian syndrome hereMyo-inositol for PCOS fertility egg qualityNew research published in the journal European Review for Medical and Pharmacological Sciences in May 2012 found that DCI and myoinositol was more effective than myoinositol alone in overweight women with PCOS.
The paper concluded with the recommendation that the combined administration of MI and DCI should be considered as the first line approach in PCOS overweight patients, being able to reduce the metabolic and clinical alteration of PCOS and, therefore, reduce the risk of metabolic syndrome.  


More Information:

Nordio M, Proietti E.  The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone.  Eur Rev Med Pharmacol Sci. 2012 May;16(5):575-81. PMID:22774396

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New research finds genetic defect in polycystic ovarian syndrome PCOS

DNA strandsResearchers have discovered for the first time, a genetic defect present in a type of microRNA in the fat cells of both women with PCOS and women with insulin resistance.  The discovery paves the way for the development of new, targeted therapies to address the cause of both PCOS and insulin resistance.  The research was published in the current issue of the journal Diabetes, and accompanied by a press release by the Medical College of Georgia, issued on Mar. 19, 2013.

A group of tiny RNA molecules with a big role in regulating gene expression also appear to have a role in causing insulin resistance in women with polycystic ovary syndrome and, perhaps, in all women, researchers report.  

MicroRNAs (miRNA or ?RNA) are single-stranded RNA molecules of 21-23 nucleotides in length, which regulate gene expression. miRNAs are encoded by genes from whose DNA they are transcribed but miRNAs are not translated into protein.

Research in the journal Diabetes, indicates that high activity levels of a microRNA called miR-93 in fat cells impedes insulin’s use of glucose, contributing to PCOS as well as insulin resistance, said Dr. Ricardo Azziz, reproductive endocrinologist and PCOS expert at the Medical College of Georgia at Georgia Regents University.

“This is one of the first reports of a defect that may occur both in women who are insulin resistant and, in particular, in women with PCOS,” said Azziz, the study’s corresponding author. “Identifying this molecular mechanism helps us understand these common conditions better and points us toward targeted therapies to correct these problems in women.”

PCOS affects about 10 percent of women, though some estimates put that figure as high as 25 percent.  The condition appears to be more prevalent in lesbian women than in heterosexual women, though it is not known why this is.  Polycystic ovarian syndrome is characterized by excess levels of male hormones which are triggered by excess levels of insulin which act upon the theca cells of the ovaries stimulating them to produce testosterone, irregular ovulation and menstruation which can lead to infertility and is associated with an increased risk for insulin resistance, which can lead to diabetes and heart disease.  PCOS is the leading cause of female infertility and the disease greatly increases the risk of premature cardiovascular disease including heart attack and stroke.

Researchers looked at fat cells from the lower abdomen of 21 women with PCOS and 20 controls. In all the women with PCOS, they found over expression of miR-93 and decreased expression of GLUT4, a key protein that regulates fat’s use of glucose for energy.  GLUT4 is the major transporter for glucose uptake into the cells and in many tissues in the body it is made available in the plasma membrane of the cell through the action of insulin.  When GLUT4 does not respond sufficiently to insulin, insulin resistance occurs, along with the cascade of metabolic and hormonal disturbances that ensue.

GLUT4 expression was lowest in the women with PCOS who also were insulin resistant. They also found the expression was low in members of the control group who were insulin resistant.  Fat, a large organ in even a thin individual, is where a lot of glucose usage via insulin occurs, with muscle being another major utilizer of insulin-mediated glucose.

“Low levels of GLUT4 in fat appear to be affecting insulin resistance in general and to have a more dramatic impact in PCOS,” Azziz said. MiR-93 was known to impact GLUT4 in other cell types and to have a role in reproduction, infertility and lipid metabolism. “There has been no clear mechanism to describe insulin resistance in PCOS and we believe this is one of the pathways,” said Dr. Yen-Hao Chen, cell biologist at MCG and the study’s first author.

Interestingly, the investigators found that two other microRNAS – miR-133 and miR-223, which are known to regulate GLUT4 expression in heart muscle cells – also were over expressed but only in the fat cells of PCOS patients, Chen said. This exclusivity implicates the tiny molecules in the underlying condition of PCOS, Chen said. The researchers don’t know yet if the two are related to miR-93. “We are just beginning to understand the role of these small molecules in PCOS and insulin resistance and much work remains to be done,” Azziz said.

Follow up studies include better understanding just how microRNAs impact GLUT4, identifying other microRNAS that do – including looking further at miR-133 and 223 – and identifying what factors impact the tiny RNA molecules.

Humans use both insulin and non-insulin related mechanisms to use blood sugar, or glucose, as an energy source.  Dr Azziz and his colleagues also published research just last month which investigated the relationship between insulin-mediated and non-insulin-mediated glucose uptake in PCOS patients compared to healthy controls.

The results, published in Journal of Clinical Endocrinology & Metabolism, showed that women with PCOS have defects in both mechanisms. In fact, PCOS women who had the most difficulty controlling glucose via insulin were also the ones with the greatest declines in their ability to use non-insulin approaches. More typically, when insulin resistance increases, the body’s non-insulin dependent usage increases, apparently to help compensate.

 Polycystic ovary syndrome appears to cause a sort of double jeopardy for those struggling the hardest to control blood sugar levels, researchers report.

Humans use insulin and other non-insulin mechanisms to convert blood sugar, or glucose, into energy and control levels in the blood, where it becomes a destructive force.

The study compared 28 healthy women to 28 women with PCOS and showed the latter have declines in both approaches, said Dr. Azziz.

Most surprising was the finding that the PCOS women who had the most difficulty controlling glucose via insulin were also the ones with declines in their ability to use non-insulin approaches. More typically, when insulin resistance increases, the body’s non-insulin dependent usage increases, apparently to help compensate. In these women, non-insulin activity was essentially unchanged except in those with the most insulin resistance, where it dropped.

“Women with PCOS who have the highest levels of insulin resistance, the greatest difficulty controlling their sugar and the highest risk for diabetes, appear to have a double defect in how glucose is controlled, which affects both the mechanisms that use insulin and those that do not,” Azziz said.

While the amount of fat around the internal organs, called visceral fat, predicted the degree to which insulin had difficulty controlling glucose, the regulation of glucose by non-insulin means was more closely associated with the amount of fat under the skin, or subcutaneous fat.

“If the fat is not as sensitive to insulin, that obviously means blood sugar levels, and probably fat and cholesterol levels as well, increase and the pancreas responds by producing more insulin,” Azziz said. “Fat abnormalities can have a tremendous impact on how we feel and how we function.”

The body uses insulin to convert sugar into energy for the cells in response to eating, stress or other acute causes of blood sugar increases. Fat is a big user of this approach. However, some tissues, such as the brain, red blood cells and adrenal gland, don’t require insulin to convert glucose to energy.

“That’s one reason why regulating only insulin does not cure diabetes,” said Azziz, noting that when fasting, about 80 percent of the body’s glucose usage occurs independent of insulin.

Next steps include understanding the molecular mechanisms behind these significant differences in how PCOS affects glucose usage, Azziz said.

The study concluded that increased general obesity, high levels of subcutaneous fat and hyperandrogenism or the symptoms resulting from high levels of male hormones such as hirsutism, male pattern baldness and acne are primary predictors of the deterioration of of the body’s ability to utilise glucose by any means.

More Information:

Chen YH, Heneidi S, Lee JM, Layman LC, Stepp DW, Gamboa GM, Chen BS, Chazenbalk G, & Azziz R. (2013) miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of Polycystic Ovary Syndrome patients and women with insulin resistance. Diabetes. PMID: 23493574

Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA. (2011) Insulin effects in muscle and adipose tissue. Diabetes Research and Clinical Practice. PMID: 21864752

Ezeh U, Pall M, Mathur R, Dey D, Berman D, Chen IY, Dumesic DA, & Azziz R. (2013)Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females.The Journal of clinical endocrinology and metabolism. PMID: 23450052


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Women wanted to participate in Indiana University study into PCOS


What is PCOS or Polycystic Ovarian Syndrome?

The Department of Obstetrics and Gynecology at the Indiana University School of Medicine is seeking healthy women ages 18 to 40 for a research study to better understand polycystic ovary syndrome.  In an interview with Mary Hardin of Indiana University on Feb. 2 Mary explained that the study was proving difficult to recruit for, despite offering some significant benefits to participants.

Women who have PCOS may be eligible to receive a medication to treat PCOS for 12 weeks during the study and all women who offer their participation will receive compensation for their time, as well as the opportunity to help scientists better understand PCOS and help those women who suffer from the condition.

Two different profiles of women are being sought for study participation:

  • Women with polycystic ovary syndrome who have infrequent periods and a body mass index from 18 to 25.  This equates to being in the normal weight range for height.
  • Women who do not have polycystic ovary syndrome to serve as controls who have regular periods and a body mass index from 30 to 40.  This equates to being in the obese range for weight in comparison to height.

Volunteers cannot be currently pregnant or be on hormonal birth control.

The study involves a screening visit, two admissions to the Indiana University Clinical Research Center for blood draws during a cream challenge test, a glucose tolerance test and an ovarian stimulation test.

Women with polycystic ovary syndrome may also be eligible to receive a medication in a 12-week treatment arm of the study.

For additional information, contact Tammy Garrett, R.N., at 317-944-7037, or

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Soup makes you feel fuller by raising blood sugar levels quickly

Soup has long been the friend of those who are trying to lose weight.  Much research has confirmed that people who begin a meal with soup, consequently eat less calories at that meal than those who don’t eat soup and that they feel fuller afterwards.  New research published in the January 2013 issue of the European Journal of Clinical Nutrition, which was published Jan. 10, has found out why.  Soup raises increases the blood sugar more quickly than other foods, making sugar and other nutrients available to the body more quickly.

Researchers from the Functional Food Centre, Oxford Brookes University, Headington, Oxford, UK in conjunction with the Brenner Centre for Molecular Medicine in Singapore and the Physiology Department of the School of Medicine at the National University of Ireland in Galway studied 12 volunteers and their responses on three different occasions to three different types of meals – a typical solid meal, a chunky soup and a smooth soup.

The partipants then recorded how full they felt and had their blood sugar and the time it took their stomach to empty from the meal measured, using standard tests.

The smooth soup took the longest to leave the stomach, followed by the chunky soup with the solid meal taking the longest.  The smooth soup had the greatest effect on blood sugar levels, raising blood sugar by an average of 87 mmol/l/minute, followed by the chunky soup at 65.4 mmol/l/minute and the solid meal coming in at 61.6 mmol/l/minute.
The researchers concluded that the smooth soup induced greater fullness compared with the solid meal because of a combination of delayed gastric emptying leading to feelings of gastric distension and rapid accessibility of nutrients causing a greater glycaemic response.y participants, in line with the findings of previous studies, reported feeling most full after the smooth soup than the other two meals.

This is something that people who are following a low carbohydrate diet should take into consideration when choosing the ingredients for their soups.  Many people choose a low-carbohydrate lifestyle in order to minimise disruption to insulin and blood sugar levels.  Eating smooth soups which have even a moderate amount of carbohydrate in them may be detrimental to blood sugar and insulin control, particularly if the soups contain ingredients like pumpkin, sweet potato or potato.

Part of the reason why soups help people to feel fuller after a meal is that they sit in the stomach for longer, making the stomach feel distended which triggers feelings of fullness and hormones associated with satiety.  Another reason that they trigger a feeling of fullness is that the nutrients contained in the soup require very little digestion and are almost immediately available in the bloodstream.  In some instances this is a good thing, and soups are definitely something that can easily play a significant part in a healthy, low-carbohydrate diet, just be careful to consider the glycaemic response when choosing ingredients.


Clegg ME, Ranawana V, Shafat A, & Henry CJ. (2013) Soups increase satiety through delayed gastric emptying yet increased glycaemic response. European Journal of Clinical Nutrition, 67(1), 8-11. PMID: 23093339

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Diindolylmethane (DIM) and PCOS: Is there a benefit?


DIM is a phytonutrient which is formed when indole-3-carbinol (I3C) is broken down.  I3C can be found in cruciferous vegetables such as those in the Brassica family like red cabbage, kale, broccoli, Brussel sprouts and cauliflower.  Diindoylmethane derives its name from its molecular structure, two indole groups attached to a methane group.  It is primarily an oestrogen regulating compound, having the ability to either increase or decrease oestrogen synthesis depending upon the dose.  In addition to its effects on oestrogen metabolism, DIM is also being studied for its anti-inflammatory effects, anti-cancer properties and its ability to stimulate the immune system.  In particular it may offer some benefit to diseases which are caused by the human papilloma virus or HPV, such as cervical dysplasia and respiratory papillomatosis.  It’s anti-cancer properties and cancer-preventative properties are related predominantly to its effect on regulating the hormones oestrogen and testosterone, affecting the development of hormonally-driven cancers such as those of the breast, prostate, ovaries and uterus.

DIM or diindolylmethane has been found to improve estrogen metabolism by altering liver function in a way which increases the rate at which oestrogens are metabolised into inactive forms, thus clearing excess from the body, which is generally beneficial in PCOS as most women with the condition also have a relative oestrogen dominance.  It also blocks some effects of oestrogen, though it may increase others.  It is also an anti-androgen, reducing the amount of testosterone in the body, which is also usually a hallmark feature of PCOS.

 ”We have focussed our attention on indole-3-carbinol, a compound found in cruciferous vegetables, and its further metabolites in the body, diindolylmethane (DIM) and indolylcarbazole (ICZ), because of its relative safety and multifaceted activities. It has been shown that it induces CyP4501A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. In addition to these indirect effects as a result of altered estrogen metabolism, indole-3-carbinol has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients. All of these responses make the study of its behavior as a therapeutic agent of considerable interest.”  Bradlow et al, 1999

Because cooking reduces the bioavailability of DIM in foods through destruction of the myrosinase enzyme which is stored in vegetables and converts I3C into DIM, a supplement may be beneficial in moderate doses, however, in the first instance increasing the amount of Brassicas in the diet should be considered.  It should be noted, that whilst DIM has been found to inhibit the aromatase enzyme in small doses, preventing the conversion of testosterone into oestrogen, converting potent forms of oestrogen into less potent forms and reducing the effects of oestrogen excess on the body, in higher doses it can actually increase the activity of the aromatase enzyme, increasing oestrogen synthesis and the effects that oestrogen has on the human body.

The human intestines also produce small amounts of the enzyme required to convert I3C into DIM, so even cooked Brassicas will provide some DIM.

DIM may assist in managing some of the symptoms of PCOS which are due to oestrogen dominance, however, it is only an auxiliary treatment.  Addressing the root cause of the oestrogen dominance should be of primary importance in treating PCOS.  The hormonal abnormalities which present in PCOS generally result from insulin resistance, which then disrupts other hormones.


Acharya A, Das I, Singh S, & Saha T. (2010) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.Recent patents on food, nutrition & agriculture, 2(2), 166-77. PMID: 20653562

Bradlow HL, Sepkovic DW, Telang NT, & Osborne MP. (1999) Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Annals of the New York Academy of Sciences, 204-13. PMID: 10668495

Castañon, A.; Tristram, A.; Mesher, D.; Powell, N.; Beer, H.; Ashman, S.; Rieck, G.; Fielder, H. et al. (2011). “Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: Double-blind, randomised, controlled trial”British Journal of Cancer 106 (1): 45–52. PMID 22075942

Chen I, McDougal A, Wang F, & Safe S. (1998) Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis, 19(9), 1631-9. PMID: 9771935

Chen I, Hsieh T, Thomas T, & Safe S. (2001) Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene, 262(1-2), 207-14. PMID: 11179685

Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, & Bjeldanes LF. (2004) Pilot study: effect of 3,3?-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutrition and cancer, 50(2), 161-7. PMID: 15623462

Ge X, Yannai S, Rennert G, Gruener N, & Fares FA. (1996) 3,3?-Diindolylmethane induces apoptosis in human cancer cells. Biochemical and biophysical research communications, 228(1), 153-8. PMID: 8912651

Gong Y. Sohn H. Xue L. Firestone GL. Bjeldanes LF (2006). “3,3?-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cells”. Cancer Research 66 (9): 4880–4887. PMID 16651444

Kim YS. Milner JA (2005). “Targets for indole-3-carbinol in cancer prevention”. Journal of Nutritional Biochemistry 16 (2): 65–73. PMID 15681163

Le HT, Schaldach CM, Firestone GL, & Bjeldanes LF. (2003) Plant-derived 3,3?-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. The Journal of biological chemistry, 278(23), 21136-45. PMID: 12665522

Lord RS, Bongiovanni B, & Bralley JA. (2002) Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites.Alternative medicine review : a journal of clinical therapeutic, 7(2), 112-29. PMID: 11991791

McDougal A, Gupta MS, Morrow D, Ramamoorthy K, Lee JE, & Safe SH. (2001) Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast cancer research and treatment, 66(2), 147-57. PMID: 11437101

Rajoria S, Suriano R, Parmar PS, Wilson YL, Megwalu U, Moscatello A, Bradlow HL, Sepkovic DW, Geliebter J, Schantz SP…. (2011) 3,3?-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid : official journal of the American Thyroid Association, 21(3), 299-304. PMID: 21254914

Rogan EG (2006). “The natural chemopreventive compound indole-3-carbinol: state of the science”. In Vivo 20 (2): 221–228. PMID 16634522
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Why eggs make a great breakfast choice


Consuming whole eggs improves blood lipids like cholesterol and triglycerides in people with metabolic syndrome, a condition commonly associated with polycystic ovarian syndrome or PCOS according to a review of new research.

Decades of mixed messaging regarding dietary cholesterol have led to avoidance of certain foods, such as eggs, particularly among individuals who are faced with health conditions. However, a recent study published in Metabolism suggests that including whole eggs as part of a weight loss diet may have positive effects on lipoprotein profiles for individuals with metabolic syndrome.

In this study, middle-aged men and women with metabolic syndrome consumed either three whole eggs or an equivalent amount of egg substitute daily as part of a carbohydrate-restricted, weight loss diet. Although participants eating the whole eggs were consuming twice as much cholesterol as they had at the beginning of the study, the researchers observed no effects on total blood cholesterol or LDL cholesterol levels after 12 weeks on the diet. All participants, including those consuming whole eggs, had improved lipid profiles with decreases in plasma triglycerides and increases in HDL cholesterol.

“Eating egg yolks was actually associated with enhanced health benefits in these high-risk individuals,”

explains Dr. Maria Luz Fernandez, lead study author and Professor at the University of Connecticut,

“Subjects consuming whole eggs had greater increases in HDL cholesterol and more significant reductions in the LDL/HDL cholesterol ratio than those who ate the cholesterol-free egg substitute.”

PCOS can develop into metabolic syndrome

It is estimated that up to 15% of women suffer from polycystic ovarian syndrome which can develop into metabolic syndrome, an increasingly prevalent condition which can affect both men and women.  It is further estimated that 34% of Americans are affected by metabolic syndrome which is a combination of at least three of the following risk factors:

  • large waistline,
  • high triglycerides,
  • low HDL cholesterol,
  • high blood pressure, and
  • elevated blood sugar.(i)

The presence of metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. It is strongly linked to insulin resistance which also accounts for the majority of cases of polycystic ovarian syndrome, and in fact a proportion of PCOS sufferers will go on to develop metabolic syndrome or diabetes, particularly if the condition is left untreated.

A Closer Look at the Incredible Egg

The United States Department of Agriculture’s Agricultural Research Service has reported that eggs now have 14 percent less cholesterol (down from 215 mg to 185 mg) and 64 percent more vitamin D than previously thought. Naturally nutrient-rich, one large egg provides varying amounts of 13 essential vitamins and minerals, including nutrients that aren’t found abundantly in other foods, including vitamin D and choline. Whole eggs offer every essential vitamin and mineral required for a healthy human, with the exception of vitamin C.

Many of these nutrients reside in the yolk, such as lutein and zeaxanthin, which are antioxidants that may prevent macular degeneration and consequent age-related blindness. While eggs contain only small amounts of these nutrients, research shows that lutein and zeaxanthin from eggs may be more bioavailable, or better used by the body, than from more concentrated sources like supplements.

A recent study published in Food and Function found that daily consumption of egg yolks was associated with increases in plasma lutein, zeaxanthin and ?-carotene in people with metabolic syndrome, which is typically associated with low levels of these important nutrients.

Free-range is better

Eggs from free-range or organic chickens are even better for you.  Analysis of eggs from fourteen different free-range flocks in 2007 found that in comparison to battery hen eggs, they contain:

  • 34% less cholesterol
  • 1?4 less saturated fat
  • 10% less total fat
  • 50% more folic acid
  • 70% more vitamin B12
  • 40% more vitamin A
  • 2 times more omega-3 fatty acids
  • 3 times more vitamin E
  • 7 times more beta carotene
  • 13 to 21 times more omega-3 fatty acids, depending upon the study cited.

According to the University of Michigan Integrative Medicine website:

“Commercially bred chickens that stay confined in cages and eat standard feed are likely treated with hormones and antibiotics. These animals may produce eggs containing antibiotic residues. To minimize consumption of antibiotic residues and other toxins found in conventionally raised birds, buy organic eggs.”

High-Quality Egg Protein and Weight Management

Weight management is a crucial aspect of preventing and managing chronic disease such as metabolic syndrome. All-natural, high-quality protein helps build muscle and allows people to feel fuller longer and stay energized, which can assist with weight management.

In fact, an egg breakfast, compared with a bagel breakfast of similar calories, has been shown to lead to greater feelings of fullness and reduced food intake at later meals, resulting in a significant reduction in BMI and waist circumference.

Protein provides a long-lasting, sustained energy source to keep you going throughout the day.  It helps keep blood sugar levels on an even keel, instead of the spikes and troughs that occur with carbohydrate-based breakfast foods such as cereals, fruit or toast, and keeps insulin levels low.

Dr. Dixie Harms, a nurse practitioner specializing in diabetes care, suggests starting the day with a protein-rich breakfast as a good weight-management strategy, a first line of defense in preventing chronic disease.

“Management of chronic disease takes a coordinated effort with diet and lifestyle,” says Harms, “A balanced breakfast including high-quality protein plus regular physical activity can help put individuals on a path to a healthier lifestyle.”


Ervin RB. (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006.National health statistics reports, 1-7. PMID: 19634296

Blesso CN, Andersen CJ, Barona J, Volek JS, & Fernandez ML. (2012) Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome. Metabolism: clinical and experimental. PMID: 23021013

Karsten, Heather. “Pasture-ized Poultry.” Penn State Online Research,” May 2003.

Karsten, H.D. (2010-3-12) Vitamins A, E and fatty acid composition of the eggs of caged hens and pastured hens. Renewable Agriculture and Food Systems, 16(01),45-54, 13. DOI: 10.1017/S1742170509990214

US Department of Agriculture, Agricultural Research Service, 2011. USDA National Nutrient Database for Standard Reference, Release 23. Online. Available at: Nutrient Data Laboratory Home Page, Accessed December 14, 2012.

iv Goodrow, EF et al. Goodrow EF, Wilson TA, Houde SC, Vishwanathan R, Scollin PA, Handelman G, & Nicolosi RJ. (2006) Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. The Journal of nutrition, 136(10), 2519-24. PMID: 16988120. JN 2006; 136(25):19-24.

Blesso CN, Andersen CJ, Bolling BW, & Fernandez ML. (2012) Egg intake improves carotenoid status by increasing plasma HDL cholesterol in adults with metabolic syndrome.Food & function. PMID: 23128450

Leidy HJ, Lepping RJ, Savage CR, & Harris CT. (2011) Neural responses to visual food stimuli after a normal vs. higher protein breakfast in breakfast-skipping teens: a pilot fMRI study. Obesity (Silver Spring, Md.), 19(10), 2019-25. PMID: 21546927

Leidy HJ, Bossingham MJ, Mattes RD, & Campbell WW. (2009) Increased dietary protein consumed at breakfast leads to an initial and sustained feeling of fullness during energy restriction compared to other meal times. The British journal of nutrition, 101(6), 798-803. PMID: 19283886

Vander Wal JS, Gupta A, Khosla P, & Dhurandhar NV. (2008) Egg breakfast enhances weight loss. International journal of obesity (2005), 32(10), 1545-51. PMID: 18679412

Tolan, A. (1974-3-7) Studies on the composition of food. British Journal of Nutrition, 10(02), 645-200. DOI: 10.1079/BJN19740024

Lopez-Bote, C.J. (1998-5) Effect of free-range feeding on n. Animal Feed Science and Technology, 34(1-2), 389-40. DOI: 10.1016/S0377-8401(97)00180-6

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What can I use as a natural carpet cleaning solution?


What natural options exist for cleaning soft furnishings and carpets, that actually work?  Many women with PCOS are sensitive to dust, mites and the toxins produced by moulds as well as the chemicals in commercial cleaning solutions, which presents somewhat of a conundrum.  Others are particularly aware of the damage that environmental chemicals can do to delicate endocrine balances and growing bodies and wish to protect their children from the health consequences that they themselves have suffered after being exposed to hormone disrupting chemicals at a tender age.

So what, asks Melody, can you safely use to clean things with, that will do a good job?

As a general rule, I use a combination of the following for most things:

  • white vinegar
  • lemon juice or half an already juiced lemon leftover from cooking
  • sodium carbonate (washing soda, electric soda)
  • sodium bicarbonate (slightly less effective than sodium carbonate, but still useful for some things)
  • essential oils such as eucalyptus, tea tree, lemon, lemon myrtle & lavender.
  • borax
  • salt
  • laundry soap
  • dishwashing detergent

This is the recipe for the cleaning solution I use in my carpet shampooing machine when the need arises.  It makes 2L of concentrate.


  • 1.7 litres of white vinegar or 1.7 litres of tepid water
  • 3 tablespoons washing soda (also called electric soda or sodium carbonate)
  • 250 millilitres boiling water
  • 1.7 litres tepid water
  • 10 millilitres dishwashing detergent
  • 25 millilitres eucalyptus essential oil
  • 10 millilitres lemon essential oil
  • 5 millilitres tea tree essential oil
  • 2 litre bottle, preferably glass, to hold the finished solution.
To make an alkaline solution, just use water.  This is best for most general grunge and dirt in carpets as the washing soda will make an alkaline solution which very effectively strips away fat/oil based stains.  If you have mould or animal urine to contend with, use the vinegar instead of water and omit the washing soda (it has a very high pH and will neutralise the vinegar).
Method 1 (alkaline):
  1. Dissolve the washing soda in the boiling water (straight from the kettle is fine).
  2. Combine the dishwashing detergent and the essential oils in a small jug or cup, stir until combined.
  3. Add a little of the hot water and washing soda solution to thin the mixture, trying not to create bubbles.
  4. Pour the thinned solution into the bottle which already contains the 1.7 litres of water, then add more of the washing soda solution to the cup to rinse out all of the dishwashing liquid and essential oil mix.
  5. Repeat steps 3 & 4 until you have used up all the washing soda solution and everything is in one bottle.
Method 2 (acidic):
  1. Pour 1.7 litres of water into a glass 2 litre bottle.
  2. Combine the dishwashing detergent and the essential oils in a small jug or cup, stir until combined.
  3. Add a little warm water to thin the mixture, trying not to create bubbles.
  4. Pour the thinned solution into the bottle then add more warm water to the cup or jug to rinse out all of the dishwashing liquid and essential oil mix.
  5. Repeat steps 3 & 4 until you have cleaned out the dishwashing detergent and essential oil jug and the bottle is full.

You can either decant the mix into a spray bottle and spray directly on stains and leave to sit for a period of time before using just plain warm in the carpet cleaning machine, or for larger areas, add a cup of the concentrate to 2 litres of warm water in the holding tank of the machine.  If you have problems with the solution foaming too much in the recovery tank (where the dirty water winds up, not where the clean water is held), add a few drops to a teaspoon of fabric softener depending on how bad it is, or a teaspoon of salt.  Either will stop the bubbles from forming.  I don’t usually have to worry about this though.

This mix is, I think, more effective than the commercial solution that the manufacturer of my machine recommends and it definitely smells better!  As always, test on a small, inconspicuous area of your carpet before going to town on the whole house and don’t be afraid to tweak the recipe to suit your needs.  This mix is targeted towards removing stains which have an oily or fatty base, as do most, particularly on the floors, or those with a biological component.

If there are some residual stains that this mix hasn’t removed, you can try spraying with hydrogen peroxide, which is a safe alternative to bleach.  It will break down quite quickly into just water and oxygen.



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