What Are The Root Causes Of PCOS? Part 3 – Inflammation

If you haven’t already checked out my blog on the Diagnostic Criteria & Four Types of PCOS (Polycystic Ovary Syndrome), dig into that HERE. Today we’re diving into Part 3 – PCOS & Inflammation of the 4-Part series discussing The Root Causes of PCOS. I hope that understanding these root causes helps you navigate this lifelong disorder.

Check out Part 1-Insulin Resistance HERE.

Check out Part 2-Androgen Excess HERE.

Here’s a quick recap introduction. PCOS is the most common endocrine disorder in reproductive-age women. The worldwide prevalence is 5-10%. That’s SO MANY women. The association of PCOS with infertility is well studied and responsible for at least 40% of female infertility. (Krysiak R, et al. 2006)

Clues that PCOS is Lurking Behind the Scenes

• Anovulation
• Menstrual irregularity
• Hyperandrogenism
  • acne
  • androgenic alopecia (hair loss on the head)
  • hirsutism (dark, coarse hair growth on the face, chin, chest, back, and abdomen)
• Infertility
• Insulin resistance
• Obesity
• Increased abdominal adiposity
• Polycystic ovaries on ultrasound

The top four root causes of PCOS

• Insulin Resistance
• Increased Androgens (Hyperandrogenism)
• Inflammation
• Genetics

Let’s dive in!

1. Insulin Resistance and Impaired Glucose Tolerance

Check out Part 1 on Insulin Resistance HERE!

2. Increased Androgens

Check out Part 2 on Androgen Excess HERE!

3. Inflammation

What is inflammation?

Inflammation is your body’s way of protecting itself. The immune system activates inflammation by secreting special chemical signals that call in other helper immune cells or directly destroy invaders like bacteria and viruses. You’ve all acutely experienced this if you’ve had influenza. You’re exposed to the virus, your immune system recognizes the virus as something that shouldn’t be in your body, and it calls in the troops. As you’re healing, you probably feel terrible, with joint and muscle pain, headaches, and a fever. This discomfort isn’t from the virus; it’s actually the inflammatory response to the virus as your body is working to heal.

Although inflammation is a necessary protective mechanism in your body, chronic low-grade inflammation causes damage to cells, especially ovarian and egg cells (oocytes). It increases the rate at which the quantity and quality of eggs decline. Chronic inflammation on a low level can occur from poor food choices, food sensitivities, stress, blood sugar dysregulation, impaired gut health, environmental toxins, chronic infections, gum disease, excess body weight, etc.

Unfortunately, inflammation perpetuates PCOS. It worsens insulin resistance and increases the production of androgens, such as testosterone. All the things you don’t want when you have PCOS!

The most common causes of chronic inflammation in PCOS are:

• insulin resistance and the blood sugar roller coaster
• nutrient-poor diet and food sensitivity
• altered gut health
• lipotoxicity and adiposity, especially belly fat

Insulin Resistance

Insulin resistance is a common feature of PCOS, affecting 50-70% of women with this disorder. (Gonzalez 2012) I’ve discussed the topic of insulin resistance and blood sugar dysregulation at length in a previous blog, HERE, so I’m skipping a repeat in this post. Please check it out if you haven’t. Insulin resistance and blood sugar dysregulation are perpetually stoking the inflammatory fire and vice versa.

Interestingly, in leaner women with PCOS, it is the glucose spikes, often experienced in reactive hypoglycemia that are thought to be more detrimental in promoting inflammation than the continuous glucose elevations commonly seen in insulin resistance (Esposito, et al. 2002)

Nutrient poor Diet

Our dietary choices pack an impressive punch when it comes to improving health. Overwhelming evidence suggests that chronic inflammation is fueled by a variety of lifestyle elements, particularly diet. Examples of illnesses associated with upregulated inflammation from dietary choices include arthritis, asthma, cardiovascular disease, diabetes, depression, inflammatory bowel disease, metabolic syndrome, and obesity. There is now data that adds PCOS to this list, which makes nutrition and the food choices at the end of our fork a powerful therapeutic tool. (Gonzalez 2012)

Poor dietary choices increase inflammation shortly after eating, and the inflammation lasts anywhere from 4-8 hours, creating a reoccurring, compounding, chronic, low-grade inflammation on a consistent basis. (Calder PC, et al. 2011) I find this to be a profoundly empowering motivator when thinking about food options and choices. It makes the often touted saying, FOOD as FRIEND or FOE, very applicable.

The Western Diet, also known as the Standard American Diet (appropriate acronym, SAD), is generally nutrient deplete, low in fiber, high in refined carbohydrates, and loaded with unhealthy fats. This dietary pattern ultimately results in a pro-inflammatory state. (Galland L 2010)

Higher glucose consumption in PCOS induces an inflammatory state through oxidative stress and the inflammatory mediators, TNFa (tumor necrosis factor-alpha) and IL-6 (interleukin-6). Sensitivity to glucose consumption is enhanced if you also have hyperandrogenism, such as high testosterone. (Gonzalez 2012) Lower carbohydrate consumption is associated with decreased insulin resistance, lower fasting insulin, decreased androgens, and overall decreased inflammation. (Moran LJ, et al. 2013)

The Mediterranean Diet has the most research in terms of a pattern of eating that supports fertility. Further study has found that modifying this dietary pattern to include a lower carbohydrate load is actually more effective at decreasing inflammation, supporting ovulation, and improving menstrual cycle regularity. (Moran LJ, et al. 2013) More recently, the therapeutic role of the Mediterranean Diet in PCOS has been validated. (Barrea L, et al. 2019)

The Mediterranean diet is:

• plant-rich: owing to the abundant vitamins, minerals, antioxidants, and many phytochemicals
• loaded with fiber: think robust gut microbiome, regular bowel movements, and excretion of toxins
• high in healthy fats: especially omega-3s from fish and monounsaturated fatty acids from olives, olive oil, nuts, and seeds, all known to reduce inflammation and stabilize blood sugar
• moderately peppered with animal-derived proteins: helpful in stabilizing blood sugar. (Willett WC, et al. 1995)

Together this evidence suggests that women with PCOS should be advised to consume a diet that includes:

• High Amounts of Fiber
  • At least 25 grams per day
  • Non-starchy vegetables are your best bet!
  • If you’re unsure how much fiber you’re currently getting you could track it for a couple of days in a free app like Cronometer.

• Healthy Fats
  • Omega-3 Fatty Acids
    • Coldwater fish: Atlantic salmon, Atlantic herring, Atlantic mackerel, Sardines
    • Flaxseeds, Chia seeds, Walnuts
  • Omega-9 Fatty Acids
    • Almonds, Cashews, Walnuts, Avocado oil, Olive Oil
  • Monounsaturated fats
    • Olives, Olive oil, Avocados, Almonds, Hazelnuts, Pecans, Pumpkin seeds, Sesame seeds

• Lots of Plants, Especially Non-Starchy Vegetables
  • Shoot for at least 12 different plant-based foods a day and see if you can include all the colors of the rainbow.

• Moderate Protein from Plant and Animal sources
  • Include a palm-sized portion of protein with each meal.

• Stay hydrated with clean, filtered water
  • Drink .5-1 ounce of water per pound of body weight per day. If you weigh 150 pounds, you need at least 75 ounces of water each day.
  • Steer clear of bottled and plastic drinking containers!
  • Are you wondering what’s in your water? Look it up by your zip code on EWG’s Tap Water Database.
  • Need a filter, but unsure about what type to get? Check out the EWG Water Filter Guide.

Ditch the following:

• Processed and Packaged Foods
  • Non-food junk that comes in a box or bag with many ingredients, fillers, preservatives, artificial colors & sweeteners

• Fast Food

• Specific Inflammatory Oils
  • Corn oil, Safflower oil, Canola oil, Soybean oil
  • These are often used for cooking in restaurants because they are cheaper.

• Trans fat, AKA: Partially Hydrogenated oil
  • Margarine, Vegetable shortening, Processed foods
  • Even though the FDA banned trans fats (partially hydrogenated oils), they are still allowed in a few items, so check carefully.
    • crackers, cookies, cakes, frozen pies, baked goods
    • microwave popcorn
    • frozen pizza
    • fast food
    • vegetable shortening
    • stick margarine
    • coffee creamer
    • refrigerated dough products (biscuits, cinnamon rolls, croissants)
    • ready to use frosting

• Refined Carbohydrates
  • Pasta, Bread, Bagels, Pastries, Baked goods, Cookies, Candy, Chips, Crackers

• Foods with a High Glycemic Load
  • Here’s a good article on glycemic load: The Lowdown on Glycemic Load: How a Free Tool Can Improve Blood Sugar Management

• Sugary & Diet Drinks
  • Soda, Juice, Sports Drinks, & Alcohol

Food sensitivities are a source of inflammation!

Food intolerance and sensitivity is a hotly debated topic! Some people believe the only food reactions that are real are the ones that cause your throat to swell or induce a massive onslaught of hives from the acute response of immunoglobulin E (gE). Think peanut allergy! While this dramatic inflammatory response is undoubtedly a food reaction there is another less acutely catastrophic response to food that can be consistently lurking behind the scenes without your acknowledgment. This response could be contributing to chronic low-grade inflammation and PCOS.

Let me start by saying there are both immune-mediated and non-immune mediated food reactions. For example, lactose intolerance is a non-immune mediated response. Lactose intolerance is due to a deficiency of the enzyme lactase that breaks down the milk sugar lactose. The presence of lactose intolerance can undoubtedly cause a response. If you’ve experienced this, you are familiar with the gas, bloating, abdominal pain, diarrhea, or an array of other symptoms you might not generally associate with drinking milk, such as joint pain, headache, acne, eczema, runny nose, etc. All signs of the underlying inflammation created by consuming dairy when you don’t tolerate it! Assessment of lactose intolerance is available via breath testing.

Other non-immune mediated responses can cause inflammation, such as fructose malabsorption and intolerances to sucrose, histamine, salicylate, and sulfites, to name a few!

Immune-mediated but non-anaphylactic or life-threatening responses to food include immunoglobulin (Ig) production against food proteins. IgG and IgA-mediated food intolerance are believed to be caused by increased gut permeability, which permits food substances to gain access to the circulation and trigger food-specific IgG & IgA production. (Beyer K, et al. 2005, Shakoor Z, et al. 2016) These reactions are less pronounced than an allergic IgE response but still promote inflammation and symptoms that may be delayed in onset by up to 72 hours. This delay makes the identification of reactivity against specific foods very difficult.

IgG & IgA food reactions will differ from person to person but are most commonly identified in response to:

• Gluten
• Dairy
• Soy
• Eggs
• Corn
• Beef
• Citrus
• Nuts

Common reactions to food include, but are not limited to:

• postnasal drip, runny nose, sinus congestion, coughing, rapid breathing
• constipation, diarrhea, cramping, bloating, reflux, nausea, gas, burping, abdominal pain, vomiting, irritable bowel syndrome
• heart palpitations, rapid pulse
• rash, eczema, flushing, hives, acne
• headaches, migraines, numbness, tingling, joint pain, swelling, back pain, neck pain
• fatigue, foggy thinking, memory issues, moodiness, anxiety, depression, dizziness, insomnia
• And I believe a contributing factor to conditions like PCOS, endometriosis, and infertility as we know inflammation is an underlying cause!

IgG & IgA food reactions can be transient following periods of food elimination and measures to improve gut health, particularly reducing intestinal permeability. Elimination diet and specific blood tests can help with the identification of food reactions. Neither is perfect but can provide helpful information to uncover potential underlying sources of inflammation. Work with your provider to figure out what is appropriate.

Altered Gut Health

In recent years, there has been a confirmed correlation between gut microbiota and metabolic disease, of which PCOS is partially considered. The literature shows that altered gut bugs can contribute to insulin resistance, hyperandrogenism, chronic inflammation, and metabolic syndrome. This likely contributes to the development of PCOS by influencing how many calories are absorbed from your food, systemic response to bacterial toxins released by gut bugs, your ability to digest and absorb nutrients, intestinal permeability (leaky gut), and alterations of the brain-gut axis. (Zhao X, et al. 2020, Zhang D, et al. 2015) Unfortunately, women with PCOS tend to have a less diverse gut microbiota. (Torres PJ, et al. 2018) Let’s change this!

Ways to support diversity of your gut microbiota!

• Lots of Fiber, Especially From Colorful Veggies (aim for at least 25 grams per day)
  • If you’re unsure how much fiber you’re currently getting you could track it for a couple of days in a free app like Cronometer.
  • Fiber is a natural prebiotic source, meaning it feeds the beneficial bugs in your gut.
  • A PCOS mouse model showed improvements in body weight, testosterone levels, and inflammatory markers with the use of prebiotics. (Zhang Q, et al. 2018)

• Kick sugar, non-food junk, and alcohol to the curb
  • Sugar and foods with a high glycemic index or load tend to alter the gut microbiota in a way that is not beneficial, increases intestinal permeability, hyperandrogenism, and ovulation disorders. (Jakubowicz D, et al. 2013)

• Movement
  • Exercise has been correlated with increased diversity of gut bugs.
  • In women with PCOS movement has been shown to make improvements in follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone, and other androgens (Haqq L, et al. 2013)

• Fermented Foods offer a natural source of probiotics to support your gut microbiome which contributes significantly to your immunity.
  • Tip: Add 1-2 TBS of kimchi, sauerkraut, kombucha, or yogurt to your day! It doesn’t take much to get a lot of these helpful bugs. 

• Go Organic!

There are other parameters to consider when thinking about gut health (i.e., intestinal permeability, infections, malabsorption, small intestine bacterial overgrowth, etc.), but it’s way beyond the scope of this post. If you’re interested in learning more about gut health get in touch with a local naturopathic doctor or other licensed integrative practitioner.

My favorite assessment tools for gut health include:

• GI Effects Comprehensive Digestive Stool Analysis (3-Day Stool Test) by Genova Diagnostics or GI-Map by Diagnostic Solutions
• Intestinal Antigenic Permeability Screen by Cyrex Labs
• Lactulose Breath Test by Neurovanna or Genova Diagnostics

Increased Adiposity (fat cells) & Lipotoxicity

Studies investigating body composition in women with PCOS report a generally higher fat-to-lean mass ratio than women without PCOS. (Savastano S, et al. 2010) Fat tissue anywhere promotes inflammation and insulin resistance, but when the distribution is particularly centered around the belly, there is an exaggerated inflammatory response. (Ezeh U, et al. 2014, Gonzalez 2012)

There has been an expanded understanding of why adipose tissue releases inflammatory mediators, such as TNFa and IL-6. Fat tissue generally has very poor circulation. As the tissue expands with enlarging or increasing numbers of cells, the central portion of the mass loses its ability to receive a blood supply and oxygen. As this happens, the fat cells die. When cells die, your immune system normally sends in a clean-up crew to remove the debris. This crew includes a special cell called a macrophage. Macrophage are the cellular equivalent of Pac-man gobbling up all the trash leftover from the dead and dying cells. However, instead of cleaning up and leaving, they stay and start pumping out the inflammatory messengers, TNFa and IL-6. The amount of these messengers released is proportional to body mass. (Weisberg, et al. 2003) This phenomenon is known as lipotoxicity.

Even a 5% weight loss has been shown to improve PCOS parameters, including insulin resistance, hyperandrogenism, and ovulatory dysfunction. Studies show that a caloric deficit of 300-500 calories per day combined with whatever dietary pattern you are following has the most promise for weight loss. (Moran et al., 2009, 2013)

Tracking Body Composition

While weight loss has been shown to improve inflammation, it’s not an accurate measurement of body composition. The easiest at-home way to track body composition changes, especially belly fat, is the Waist-to-Height Ratio, which is also a predictor of insulin resistance.

• Waist-to-Height Ratio
  • Online Waist to Height Ratio Calculator
  • Normal =.42-.48

Can we assess for inflammation in PCOS?

hsCRP (high sensitivity C-Reactive Protein)

C-reactive protein (CRP) using a high sensitivity assay has been the most reliable marker of low-grade chronic inflammation in PCOS. This marker is produced by the liver and adipose tissue, especially belly, in response to the inflammatory cellular messengers, TNFa and IL-6. However, the reliability of this marker changes in women with lean type PCOS if abdominal adiposity is lower. There also continues to be debate as to whether circulating inflammatory markers, such as CRP, can adequately reflect inflammation in tissue compartments, such as abdominal adipose tissue, in response to inflammatory changes. (Minihane AM, et al. 2015)

I feel like hsCRP is important to keep track of when you have PCOS. However, you might consider some of the additional tests I’ve mentioned throughout this post that may help understand the root causes of inflammation and also help determine potential therapeutic options.

Nutrients & Herbs That May Help Reduce Inflammation in PCOS

• Resveratrol
  • (Brenjian S, et al. 2020)

• Specialized Pro-Resolving Lipid Mediators (SPMs)
  • (Regidor P, et al. 2020)

• Omega-3 Fatty Acids: EPA + DHA
  • (Tosatti JAG, et al. 2021)

• Turmeric
  • (Mohammadi S, et al. 2017)

• Vitamin D
  • (Akbari M, et al. 2018)

You Don’t Have To Do This Alone!

If you have PCOS or think you may have PCOS, consider working with a holistically-minded provider who can offer a thorough assessment of your whole health and provide personalized therapeutic options. You don’t have to do this alone! 🙂  

I always hope that my posts are supportive of your journey. There are additional resources and references below. Leave me a comment, check back often, and reach out if you need a partner in this process! Thanks so much for reading. 

If you haven’t done so already, check out my other PCOS Related Blog Posts! Part 4 of the Root Causes of PCOS Series will be posted soon.

Disclaimer: This website and post include general information about nutrition, health, and fertility. This content is not medical advice. It is not a replacement for medical advice, diagnosis, or treatment of any health condition or illness. With that said, if the reader or any other person has a medical condition, concern, or illness, they should consult with their personal doctor or another appropriately licensed healthcare provider. The reader should also never disregard professional medical advice or delay in seeking advice because of something discussed in this information. It is imperative to consult your doctor or another appropriately licensed healthcare provider before implementing any changes to your diet, fitness routine, lifestyle, medications, or nutritional supplements.

Information provided in this document and the use of any products or services related to this document by you does not create a doctor-patient relationship between you and Tamara Darragh, ND. 

Statements regarding dietary supplements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease.

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References

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