Unraveling the Common Thread: Inflammation in PCOS and MTHFR

I’ve invited a knowledgeable colleague of mine, Brian McGee, creator of Primal Build Essential Amino Acids, to tell you about something that may be a real game changer in the treatment of PCOS-related mental health symptoms. It may also be a huge factor in reducing many of the physical symptoms of PCOS. This is the first of three articles describing the issue and solution.


What on earth is MTHFR (Methylenetetrahydrofolate Reductase)? If you haven’t heard of it yet, it’s critical that you know about it, since 30 – 40% of Americans are likely to have this genetic defect, which contributes to mood disorders like depression and anxiety. Polycystic Ovary Syndrome (PCOS) is also a big contributing factor in mood disorders. Both PCOS and the MTHFR mutation are distinct conditions, but they converge in a significant way: both lead to increased systemic inflammation. This article will explore how this shared aspect can affect both diagnosis and overall health in a significantly negative way.

The Role of Inflammation in PCOS and MTHFR

Let’s talk briefly about inflammation. In and of itself, inflammation isn’t a bad thing. In fact, it’s a critical tool for homeostasis (balance in the body).Like anything, too much of a good thing is never good. For example inflammation, like a fever, helps the body combat an infection. However, as we all learned during the pandemic, too much inflammation could be deadly – AKA, the Cytokine Storm. So in our conversation here, we’re going to look at elevated inflammation that isn’t immediately life threatening. In this respect, we’ll refer to this as systemic inflammation. The effects of this are more long term consequences. Additionally, there are usually very little signs or symptoms for the individual to notice early on. By the time your body starts giving you signals that something is wrong, years or decades have passed since inflammation levels rose. The last point I’d like to make on this is the trajectory systemic inflammation takes will vary a great deal among individuals. I like to characterize it as “breaking the weak link”.

Invariably, the weak links are what will break down over time from systemic inflammation. What those weak links are depends entirely on lifestyle and genetics. This is true for all people. Now moving forward into the specifics on individuals with PCOS, MTHFR, or both, the weak links are more identifiable and will affect you from day one.

Systemic inflammation is a critical factor in both PCOS and MTHFR. Symptoms of inflammation, such as fatigue, pain, and metabolic disturbances, may be attributed to one condition when the other is also present, or both might be affecting the individual. The similarity in inflammatory responses could lead to diagnostic confusion.

In PCOS, inflammation exacerbates hormonal imbalances and can contribute to insulin resistance. In the case of MTHFR mutation, inflammation arises from impaired methylation processes. Methylation is where a methyl donor molecule is added to B-Vitamins and thus makes them “active.” Without this, the B-Vitamins cannot play their role in the building of protein, and just as important the breakdown of homocysteine after protein has been synthesized. You may also notice a common PCOS symptom: endless fatigue. In both cases, B-Vitamins play pivotal roles in wellness outcomes. For PCOS, B-vitamins help with hormone imbalances and in MTHFR, they help with lowering homocysteine levels, if they are methylated types. It’s important to know that only methylated types of B-vitamins will be effective in improving brain health and processes. Elevated systemic inflammation can lead to increased risks of certain other conditions which are easily diagnosed such as cardiovascular disease. However, often the clues can be less obvious. The one thing we can know for certain is that having elevated levels of inflammation throughout the body causes a major problem. Your body loses its ability to sense accurately what is going on with all the metabolic functions. I have explained this to my clients like this: “It’s not that your hormones are out of balance, as far as your body is concerned. In fact they are probably spot-on, given the information it was provided. The problem is that inflammation interferes with accurate sensing.”


Misdiagnosis and overlapping sets of symptoms can complicate treatment of PCOS. Recognizing the role of inflammation is crucial for accurate diagnosis and effective management. Having a plan that incorporates regular assessment of systemic inflammation is critical. Being able to put out the fire requires being able to see the smoke. Having tools that let you see where your inflammation levels are rising is a good thing. The next post will delve deeper into another commonality of the two conditions: elevated homocysteine levels.

Brian McGee

With over three decades of dedicated experience, Brian McGee stands as a vanguard in structural integrative massage and cranial sacral therapy. A Certified Massage Practitioner (CMP) from California, Brian McGee has revolutionized client rehabilitation post-conventional surgeries with bespoke biomechanical exercises, outperforming traditional physical therapies.

Delving deep into the realms of nutrition and metabolic functions, Brian McGee recognizes the often overlooked elements vital for wellness. This insight has culminated in the pioneering development of a sports nutrition formula, designed to rectify prevalent deficiencies in the market. His profound commitment to enhancing metabolic function and overall health is evident in every aspect of his work.

Through his practice, Brian not only restores physical vitality but also empowers clients to achieve their ultimate wellness goals, embodying a true testament to the power of integrated healing and nutritional foresight. Join Brian on a journey to optimal health, where innovative therapy meets nutritional excellence.