The Inflammatory Response & Reproductive Health: How Can Nutrition Help?

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The female reproductive tract contains an intricate ecosystem of host cells, immune components, microorganisms, and metabolites, which are essential to maintaining homeostasis.1 This balance can become dysbiotic if it shifts toward inflammation while under the influence of certain factors like stress, disease, pathology, lifestyle choices, and others.1

Inflammation brings forth a complex narrative of intra- and extracellular events, and research suggests that chronic inflammation can foster the development of a variety of reproductive health disorders, including endometriosis and polycystic ovary syndrome (PCOS).2-5 As well, inflammaging, a term that encompasses the concept of a feedback loop between two triggering factors—aging and inflammation—can negatively predispose the woman to reproductive dysfunction, infertility, and obstetrical diseases during pregnancy.6 What dietary interventions may improve reproductive health outcomes in women?

Inflammatory Gynecological Conditions

Inflammatory processes play critical roles in a normal pregnancy, and a level of inflammation is required for successful ovulation, implantation and placental formation, retention of the semi-allogeneic fetus, protection against external pathogens for the fetus, and more.3 However, aberrant inflammation can lead to conception and pregnancy complications. Inflammatory reproductive disorders involve complex immune responses related to the kinetics of immune cells, the secretion of cytokines and chemokines, and the activation of inflammasomes.3

Inflammaging: “Inflammaging” describes the low-grade, chronic, systemic inflammation in aging in the absence of overt infection.7 It is the long-term result of the chronic physiological stimulation of the innate immune system, which can become damaged during aging.7 Several lifestyle and nutritional factors, environmental insults, and long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging.6 These effects may contribute to unwanted pregnancy outcomes like pre-term birth and low birth weight.6,8

While fertility naturally declines as women age, higher levels of inflammation may lead to a faster reduction of the ovarian reserve and is associated with poor quality embryos.6 Researchers hypothesize that inflammaging may play a role in ovarian senescence and premature ovarian insufficiency and may even negatively impact IVF treatments. Beyond the womb, this chronic proinflammatory state may also induce epigenetic modification and metabolic reprogramming in the fetus and the placenta, making the offspring more susceptible to future non-communicable diseases.6

Polycystic Ovary Syndrome: Polycystic ovary syndrome (PCOS), a major cause of infertility, is characterized by polycystic ovarian morphology, ovulatory dysfunction, and systemic low-grade inflammation.3 Inflammatory markers perform a substantial part in managing the functions of the ovary and are associated with PCOS pathogenesis.4 The interplay between inflammatory cytokines in the PCOS ovary strongly implies that inflammation is one of the most potent risk factors of PCOS;4 several studies have found that women with PCOS are more likely to have elevated levels of CRP compared to those without the condition.9

Endometriosis: Endometriosis, an inflammatory condition associated with debilitating chronic pelvic pain, is estimated to affect 6-10% of women of reproductive age and can be detected in up to 50% of women seeking treatment for infertility.5 It is defined by the presence of endometrial glands and stroma outside of the uterine wall and is associated with an inflammatory response.10

Upon implantation of ectopic endometrial fragments, macrophages and neutrophils are first recruited, secreting numerous cytokines and growth factors with proinflammatory, chemotactic, and angiogenic properties, including TNF-?, IL-1, IL-6, IL-8, and vascular endothelial growth factor.2 An excessive amount of retrograde menstruation and subsequent iron overload overwhelm macrophage physiology, triggering aberrant inflammatory signaling and impaired phagocytic potential. This local inflammatory environment leads to the development and progression of lesions and angiogenesis.2

Anti-Inflammatory Diets for Reproductive Health

Lifestyle—including caloric intake and diet composition in terms of vitamins, protein, lipids, carbohydrates, and mineral content—is particularly important for women with inflammatory reproductive conditions.11 The Mediterranean diet is a well-known plant-based diet that may reduce hsCRP and other inflammatory markers.12 Polyphenols and flavonoids of plant origin have antioxidant and anti-inflammatory properties and thus play a critical role in the Mediterranean diet. This diet is also high in n-3 polyunsaturated fatty acids (PUFA) and fish oil, which are commonly used to decrease the inflammatory burden.13

Related to reproductive health, studies suggest that in pregnant women, a higher adherence to the Mediterranean diet is associated with a significantly reduced risk of having an overall preterm birth and low birth weight baby compared to women with lower adherence to the diet.14 These women also have significantly reduced odds of delivering small-for-gestational-age babies compared to women with a lower adherence to the Mediterranean diet.15,16

A 2021 systematic review and meta-analysis of cohort studies suggests that a higher maternal adherence to a healthy diet is associated with a reduced risk of gestational hypertension by 14% (P<0.001), maternal depression by 40% (P=0.004), low birth weight by 28% (P=0.001), and preterm birth by 56% (P<0.001) compared to a lower adherence to the diet.17 In addition, the researchers saw higher gestational weight gain (Hedges’ g: 0.15; P=0.01) and birth weight (Hedges’ g: 0.19; P=0.007) in women who had a higher adherence to the Mediterranean diet compared to a lower adherence.17

In women with inflammatory gynecologic conditions, the results of diet are also significant. A 2022 prospective birth cohort study of 3,278 Japanese women with endometriosis suggests that the odds of having a preterm birth during the preconception period (<34 weeks) in the group exposed to an anti-inflammatory diet was 75% lower than those who consumed a more proinflammatory diet (95% CI, 0.07-0.83).18 Furthermore, for these women, the odds of having a child of low birth weight (<1,500 g) was 93% lower for women in the anti-inflammatory diet group compared to the proinflammatory diet group (95% CI, 0.01-0.60).18

In a recent study by Mei et al, 59 obese women age 16-45 years with PCOS were randomly allocated one of two energy-restricted diets (<1,400 Kcal/day), the Mediterranean low-carb diet or the low-fat diet, for a period of 12 weeks.19 At the end of the trial, women who underwent the Mediterranean low-carb diet had a more statistically significant improvement in weight and body measurements, sex hormones, and metabolic parameters. In addition to these developments, more than 70% of participants restored their normal menstrual cycle (irrespective of diet) by the end of the trial.19

Clinical Considerations

Nutrition-based interventions are fundamental components of many functional medicine strategies. These personalized treatments may include modifiable therapeutic food plans that address nutritional imbalances. Patient-practitioner collaboration, a foundational approach in the functional medicine model, is essential for successful implementation and sustainability of these plans. Assessing the readiness of a patient, understanding their specific needs and situation, and identifying any barriers that may impact sustainability of a nutrition treatment strategy may be essential for enhancing patient engagement and improving long-term success.

As functional medicine practitioners know, nutrition is an important factor in many personalized therapeutic strategies, and IFM offers many tools for delivering personalized and effective nutrition interventions. For example, the IFM Toolkit contains the assessment tool “Readiness for Change” to help practitioners gauge and support a patient’s readiness for modifying lifestyle habits and behaviors. In addition, IFM offers a range of modifiable therapeutic food plans.

For in-depth instruction on how to personalize IFM’s suite of therapeutic food plans in order to best meet the needs of clients and patients, explore IFM’s online course, Therapeutic Food Plans: A Component of Personalized Nutrition. For more information about inflammaging and other inflammatory conditions, IFM’s Hormone Advanced Practice Module will clarify how to approach hormonal dysregulation, with emphasis on comprehensive hormonal assessment and an integrative approach to treatment of hormonally driven conditions.


Related Articles

Functional Fertility, Pregnancy, and Fetal Health

PCOS: Treatment and Care

Endometriosis: Root Causes & Lifestyle Interventions


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