Infertility and Syndrome X, aka the Metabolic Syndrome

Some of the most compelling pieces of evidence that nutrition plays a pivotal role in the condition called infertility are recent research articles linking the metabolic syndrome, or Syndrome X, to infertility.

Syndrome X is characterized by the following: insulin resistance, hyperinsulinemia and hyperglycemia, increased triglycerides, decreased HDL, increased LDL, reduced fibrinolysis, hyperuricemia and the classically associated diseases of type 2 diabetes, coronary artery disease, hypertension and obesity.1

If patients have three or more of the following risk factors, they are said to be suffering from Syndrome X.2

  1. Fasting blood glucose of ≥ 100 mg/dL
  2. Triglycerides of ≥ 150 mg/dL
  3. HDL cholesterol
  4. Blood pressure of ≥130/85 mmHg
  5. Waist circumference of >40 inches for men and >35 inches for women

Infertility, which is defined as the inability of a heterosexual couple to conceive after 12 months of unprotected sex, or 24 months internationally, affects 5 million women or 10-15% of couples. Idiopathic infertility, in which no cause is identified, affects 1 million or 20% of couples who are infertile.3 For the sake of brevity, this article only discusses the issues associated with female infertility, however the metabolic syndrome affects men just as much as women in every age group studied. Issues of male infertility or subfertility include decreased sperm counts, decreased sperm motility and abnormal sperm morphology. These issues are sometimes caused by and definitely exacerbated by Syndrome X as well.

In a study of the prevalence of Syndrome X according to age group, in women and men aged 30-39, 10-15% were affected.4 Considering the age group of professional women waiting to become pregnant, I think of women in their 30’s and 40’s. The statistic noted above that fertility issues affect 10-15% of all couples, and the incidence of metabolic syndrome in women and men aged 30-39 being 10-15% may not be coincidental at all. In women and men aged 40-49, Syndrome X affects a staggering 20-25%.(ibid)

To link the statistics of infertility and the prevalence of Syndrome X among women and men aged 30-39, and 40-49 makes great sense.

Some of the effects of Syndrome X on fertility include polycystic ovary syndrome (PCOS), the number one cause of female infertility.12

What is polycystic ovary syndrome (PCOS)?

Ovaries contain follicles with an egg in each one of them. At ovulation a follicle matures and releases an egg. PCOS is a condition in which immature follicles in the ovaries clump together into bunches called cysts, and mature eggs are released into the cysts. The eggs never travel through the fallopian tubes towards the uterus where they may be fertilized. Women may therefore not get a period for many months. She is therefore anovulatory, or she doesn’t ovulate, at least not regularly.

Women with PCOS are well known to have other health problems, such as abnormally high levels of insulin, obesity, high blood pressure, and heart disease.12 These constitute elements of Syndrome X.

What causes high levels of insulin?

Inflammation in the body occurs as a result of the nutrients, especially in combination with a lack of essential nutrients, in the foods we consume in our diet. This inflammation causes insulin resistance or insulin insensitivity.16 Increasing body fat activates an inflammatory response in the fat cells and liver, which stimulates the release of more inflammatory chemicals. These fuel insulin resistance in skeletal muscles and other organs, and plaque formation (atherogenesis) in blood vessels.21

It is safe to say that if we improve the quality of the food we consume, we can reduce the degree of insulin resistance in our bodies, and hopefully reverse this metabolic state.
Why is it that fertility decreases with age?

It is established that the chances of becoming pregnant decreases with age.11 Women are born with a finite number of eggs that will be released during their lifetime. However, is it possible that the longer a woman exposes her body to chronic inflammation through years of consuming inflaming foods, the higher the chances she will develop insulin resistance, and the higher the chance she will develop fertility issues?

Syndrome X is a proinflammatory, protumor and fibrin state6 that encourages endometriosis7 another common cause of infertility. Some 30-40% of women with endometriosis have infertility, and 6-15% of women with infertility have endometriosis.13 Endometriosis is associated with increased cytokines,14 another result of the proinflammatory effects of Syndrome X.

What is endometriosis?

In endometriosis, uterine tissue which lines the inside of the uterus grows outside the uterus. The two most common symptoms are pain and infertility. This abnormal growth of uterine tissue can be a result of the reduced fibrinolysis (breakdown of fibrin) that occurs in Syndrome X.

When women menstruate, there is a normal phenomenon called retrograde menstruation. This means some blood flows backwards and out into the pelvic cavity rather than flowing through the uterus and out through the birth canal. With normal fibrin breakdown, our bodies degrade the blood in the pelvic cavity with no untoward effects. With reduced degradation of the menstrual blood backflow, the menstrual byproducts become uterine tissue outside of the uterus, and painful adhesions and scars result.

Dietary factors contribute to endometriosis (and breast cancer) via the activity of the enzyme aromatase.8 Aromatase activity is increased in Syndrome X. The presence of excessive inflammatory dietary fatty acids in our diets can increase the activity of this enzyme. (ibid)

Other causes of infertility

A third cause of infertility is autoimmune17; it causes ovarian dysfunction19 and endometriosis.20 The fact that obesity is associated with a state of aberrant immune activity and an increased risk for associated inflammatory diseases18 should come as no surprise.

An article about infertility would be incomplete without the mention of the effects of stress. The current accepted medical model of disease is bio-psycho-social. This means doctors look at the biological causes of diseases, as well as the contributory psychological and social components.

Fertility issues are noted to be the #2 or #3 causes of stress on a marriage. Stress decreases fertility because it creates high levels of circulating cortisol. The precursors for cortisol are the same ones that are needed to get pregnant and maintain a pregnancy. So the body’s resources are limited, and an automatic choice is made. The chemicals go towards cortisol production rather than towards hormones that promote fertility and a healthy term pregnancy.

Interestingly, adipokine imbalance (excess body fat as seen in Syndrome X) causes depression and sympathetic overactivity.22 Sympathetic overactivity causes a stressful chemical state in the body, or a flight-or-fight response, one a woman is definitely trying to avoid if she wants to get pregnant.

Addressing the mind-body connection, getting psychological counseling and finding ways to keep the peace within through appropriate nutritional choices, acupuncture and yoga are a powerful combination to promote fertility.

Putting it all together

So what does this all mean for women who are trying to get pregnant in their 30’s and 40’s?

In the article appropriately titled “Is there a fertility diet?”15 and others stating that evidence at present favors chronic inflammation as a trigger for chronic insulin insensitivity, rather than the reverse situation,16 we see evidence to support dietary anti-inflammatory diets.

My next articles will detail the controllable dietary factors that contribute to Syndrome X and infertility, acupuncture and yoga for fertility. These natural interventions can also assist women who are using Assisted Reproductive Techniques to achieve higher rates of desirable outcomes.

References

  1. Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: more than just syndrome X. Compar Biochem Physiol 2003; 136:95-112
  2. Wilson PW, Grundy SM. The metabolic syndrome: practical guide to origins and treatment: Part 1. Circulation. 2003. 108:1422-24
  3. Wurn BF, et al. Treating Female infertility and Improving IVF Pregnancy rates With a Manual Physical Therapy Technique. MedGenMed. 2004. June 18; 6 (2):51
  4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National heath and Nutrition Examination Survey. JAMA 2002; 287:356-9
  5. Blaha M, Elasy TA. Clnical use of the metabolic syndrome: why the confusion? Clin Diabetes. 2006; 24(3):125-31
  6. Dvorak HF. Tumors: wounds that do not heal. New Eng J Med 1986; 315:1650-59
  7. Bedaiwy MA et al. Genetic polymorphism in the fibrinolytic system and endometriosis. Obst Gynec. 2006; 108:162-168
  8. Bulun SE et al. Estrogen production and metabolism in endometriosis. Ann NY Acad Sci. 2002; 955-75-85
  9. Polotsky AJ, Houston S. Contemp Ob Gyn. 2009. Nov; 54(11): 37-8, 40, 42 (22 ref)
  10. Hays, Bethany. Infertility: A functional medicine approach. Integrative medicine. Dec 2009/Jan 2010, Vol 8, No 6.
  11. Dunphy, BC, et al. Female age, the length of involuntary infertility prior to investigation and fertility outcome. Human Reprod. 1989; 4(5); 527-530.
  12. National Institutes of Health, Eunice Kennedy Shriver National institute of Child Health and Human Development. Disorders associated with infertility. NICHD. Updated April 15, 2009.
  13. Tariverdian, N et al. Neuroendocrine-immune disequilibrium and endometriosis: an interdisciplinary approach. Semin Immunopathol 2007; 29 (2):193-210.
  14. Lawson, C et al. Increased expression of interleukin-1 receptor type 1 in active endometriotic lesions. Reproduction 2007; 133(1):265-274.
  15. Potolosky, A, Houston S. Is there such things as a “fertility diet”? Contemp OBGYN 2009 Nov; 54(11): 37-8, 40, 42 (22 ref)
  16. Grimble, RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care. 2002; 5:551-59
  17. Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol, 2005:2(9):416-422
  18. Wellen, KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005; 115:1111-19.
  19. Pires, ES, et al. Specific and sensitive immunoassays detect multi anti-ovarian antibodies in women with iinfertility. J Histochem Cytochem 2007;55(12):1181-1190. Epub 2007 Jul 24.
  20. Heyer, A, et al. Human endometriosis is associated with plasma cells and overrexpression of B lymphocyte stimulator. Proc Natl Acad Sci U.S.A. 2007;104(30):12451-12456. Epub 2007 Jul 17.
  21. Shoelson, SE, Lee Goldfine AB. Inflammation and insulin resistance. J Clin Invest, 2006;116(7):1793-801
  22. Axelsson J, et al. Adipose tissue and its relation to inflammation: the tole of adipokines. J Ren Nutr. 2005;15(1):131-6

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