PCOS research findings by Sarah Devido
Polycystic ovarian syndrome (PCOS) has increased dramatically in our practice, especially with young women. PCOS is the most common cause for menstrual irregularities and anovulatory infertility, affecting one in twenty women of reproductive age (Tremellen and Pearce 2005). We have found women who have some or all of the following symptoms may have PCOS or be in the early stages of the syndrome: bloating, swelling, excessive weight gain, hair loss, acne, loss of menstruation, and infertility.
PCOS is clinically defined by the presence of at least two of the three features: menstrual irregularity, hyperandrogenism (acne, scalp hair loss, excessive facial and body hair growth), and enlarged “polycystic” ovaries. PCOS subjects have disrupted hormones, insulin resistance and chronic low-grade inflammation. In long term PCOS patients, insulin resistance and inflammation are believed to be responsible for diabetes, metabolic syndrome and cardiovascular disease (Tremellen and Pearce 2015).
While PCOS is characterized by a chronic state of inflammation and insulin resistance, the exact mechanism triggering these conditions is not known. Genetic, neuroendocrine, and metabolic abnormalities have been proposed as explanations. But most recently, Tremellen and Pearce (2005) have proposed abnormalities in the gut, including leaky gut and gut dysbiosis (imbalances of gut microbiota), as reasons for the inflammation and insulin resistance. In fact, this is what we have seen in our practice.
Gut Dysbiosis and Leaky Gut
Gut dysbiosis and leaky gut work together to produce inflammation and insulin resistance. With gut dysbiosis, gut microbiota become unbalanced (favoring the growth of bad bacteria over good). This occurs from poor diets, i.e. a diet high in saturated fat, refined sugar and low fiber. Leaky gut occurs when the lining of the gut allows substances to pass through into the bloodstream. This is caused by a poor diet and substances such as caffeine, alcohol and antibiotics. We also note that candida, pathogenic bacteria, strep and staph can contribute to this. Once these substances are the bloodstream, the body starts an inflammatory response to them.
Tremellen and Pearce (2005) demonstrate how this occurs specifically in PCOS. The authors indicate PCOS clients are more likely to have gut dysbiosis and leaky guts. With gut dysbiosis, the bad bacteria play a role in disrupting the body’s natural microbiota. These bad bacteria have a component in their cell wall called lipopolysaccarides (LPS). When LPS pass through a leaky gut, it enters the bloodstream and activates the immune system creating an inflammatory state (Cani et al 2007a,b). This then results in receptors for insulin becoming impaired and the onset of insulin resistance (Cani et al 2007a, Cani et al 2008, Anderson et al 2007). Insulin resistance can produce all three symptoms of PCOS – menstrual irregularity, polycystic ovaries, and hyperandrogenism (Tremellen and Pearce 2015). In addition, the extra insulin produced from an inflammatory state increases free testosterone within the skin, resulting in acne and hirsutism (excessive hair growth) (Tremellen and Pearce 2015).
We have found PCOS clients to also have dysfunction in bile production. Bile
is both an excretory secretion, to eliminate cholesterol and waste products, and a digestive secretion, to promote lipid absorption in the small intestine. Interestingly, bile plays a role in estrogen metabolism, insulin resistance, and the overgrowth of small intestinal bacteria, which have been present in our PCOS clients. Estrogen dominance is the build up of estrogens in our bodies due to sub-optimally functioning liver detox pathways and the overabundance of estrogen mimickers in our food supply and environment. Estrogen dominance causes our bile to become thick and sluggish, and the bile cannot clear toxins as efficiently as possible (Lynn et al 1973).
Recent studies have shown bile acids to be important cell signaling molecules, which may activate several signaling pathways to regulate biological processes (Li et al 2013). They help regulate lipid and carbohydrate metabolism as well as inflammatory responses (Fuchs 2012, Li et al 2013). So, proper bile production is key to preventing insulin resistance.
Bile salts play a role in inhibiting the growth of bacteria in the small intestine (Hoffman and Eckmann 2006). As a result, if someone has problems with the production of bile, then this can increase the risk of developing a condition such as small intestinal bacterial overgrowth (SIBO), which can lead to bloating and constipation.
We have found PCOS symptoms can be reversed by healing the gut, replacing harmful gut bacteria with good bacteria, eliminating excess estrogen and/or testosterone, supporting liver detox pathways, and regulating insulin through supplements and diet. Supplements that have worked for our clients are the following: methyl folate (in the case of impaired methylation) L-glutamine(supports tight junctures of the small intestine), probiophage DF(supports recolonizing of good intestinal bacteria), Lipase,
(supports fat absorption) beet concentrate (helps with bile flow), l-glutamine and Quercetin help to tighten the junctures of the intestinal lining, NAC, calcium d-glutarate, D-chiro-inositol and myo-inositol. D-chiro-inositol and myo-inositol are ground breaking supplements that have clinical evidence in restoring ovulation, reducing androgens, and managing insulin levels. Studies in women with PCOS show inositol deficiency may be important in insulin sensitive tissues and altered metabolism of insulin. A study conducted in Italy with 50 PCOS women who took myo-inositol for three months, found that plasma LH, testosterone, free testosterone and insulin were significantly reduced. In 6 months of taking myo-inositol, both hirsutism and acne decreased. The researchers concluded, “MYO inositol administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.” We have found this type of management along with healing the gut, and stopping the recirculation of estrogens to be an effective solution.
Anderson PD, Mehta NN, Wolfe ML, et al. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab 2007;92(6):2272–9.
Cani PD, Amar J, Iglesias MA, et al (a). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56(7):1761–72.
Cani PD, Neyrinck AM, Fava F, et al (b). Selective increases of bifidobacteria in gut
microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007;50(11):2374–83.
Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57(6):1470–81.
Fuchs, M. Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor as an Emerging Treatment Target. J Lipids. 2012: 934396.
Hoffmann AF, Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proc Natl Acad Sci U S A. 2006 Mar 21; 103(12): 4333–4334.
Li Y, Jadhav K, Zhang Y. Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol. 2013 Dec 1;86(11):1517-24.
Lynn J, Williams L, O’brien J, Wittenberg J, Egdahl RH. Effects of Estrogen upon Bile:
Implications with Respect to Gallstone Formation. Ann. Surg. 1973. 178(4):514-522.
Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA) – A novel theory for the development of Polycystic Ovarian Syndrome. Medical Hypotheses 79 (2012): 104–112
(need to add Teri’s citations)