MTHFR, Adrenal Fatigue and Burnout

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MTHFR, Adrenal Fatigue and Burnout

MTHFR, Adrenal Fatigue and Burnout

Dr. Doni, author of The Stress Remedy, explains how MTHFR mutations are related to adrenal burnout and chronic adrenal fatigue, as well as how to get your groove back.

Part 7 of Dr. Doni’s Series on How Genetic Mutations Affect Your Health

Today I am going to talk about the relationship between adrenal fatigue and the MTHFR mutation and what you can do to maintain and support your energy levels on a daily basis.

Fatigue is one of the top complaints I hear from patients. It usually comes along with other concerns, such as not sleeping well, aches and pains, digestive disturbances, weight gain, menstrual or menopausal symptoms, and/or allergies.

There are many potential causes of adrenal fatigue, including anemia and low thyroid function, all of which need to be considered in order to find all of the underlying causes for you. Then, knowing the cause(s), we can address them strategically.

One common tie between all causes of adrenal fatigue is involvement of the adrenal glands, the part of our bodies that responds to stress of all types, making cortisol and adrenaline, and methylation, which is the way our bodies use B vitamins. However, often adrenal function and methylation are not addressed by practitioners.

That’s why in this article, we will cover: 

  • How is fatigue related to adrenal fatigue?
  • How methylation is related to fatigue
  • Investigating the causes of fatigue
  • Creating a strategic plan
  • What can I do to start feeling better?
  • Improving your energy once and for all

How is fatigue related to adrenal fatigue?

Even though the list of symptoms can be long, fatigue is the indication that your body is depleted. And, if your body is depleted, it’s because you have been exposed to stress.

Whether you are exposed to mental, emotional, and/or physical stresses, it is the job of your adrenal glands to respond. You see, our adrenal glands are constantly adapting to the stress we are exposed to and, as they adapt, the levels of cortisol and adrenaline they produce can shift away from optimal.

As this occurs—whether your cortisol is low when it should be high (in the morning) or too high at times it should be low (evening)—you are more likely to feel tired.

I refer to imbalanced cortisol and/or adrenaline as “adrenal distress” (also known as adrenal fatigue). It can have a major effect on your overall health and well-being, and that’s why adrenal distress is one of the three problem networks I describe in my book, The Stress Remedy.

How methylation is related to adrenal fatigue

Several processes that could result in fatigue are reliant on healthy methylation.

Methylation (starting with methylfolate) is needed to produce SAM (s-adenosyl methionine), which is used to create and eliminate adrenaline. When someone with an MTHFR mutation(s) is not getting enough methylfolate, they could have higher or lower adrenaline (norepinephrine and epinephrine) levels. This could result in fatigue.

The enzymes that make and break down serotonin and dopamine also require methylation and SAM to work well, so imbalanced serotonin and/or dopamine levels can result from not having enough methylfolate. Both of these situations can affect mood and energy levels.

At the same time, histamine levels can increase when you don’t have enough SAM, making you more susceptible to allergic responses, which can cause fatigue. But as soon as we support methylation in the right way, all of these systems can improve.

You can read more about MTHFR here and about the methylation cycle here.

Investigating the Causes of Adrenal fatigue

It is important, whenever your energy is low, to evaluate the cause by doing a number of tests including:

Blood tests:

  • Anemia, low thyroid function, blood sugar issues. All are common causes of adrenal fatigue.
  • Issues related to MTHFR function such as RBC folate, Homocysteine and Methylmalonic acid. These will tell us your folate, B6 and B12 levels.

Saliva tests:

  • Cortisol. Testing your cortisol levels will tell us how well your adrenals are functioning. Whether cortisol is too low or too high, it can cause adrenal fatigue. When cortisol is low in the morning and/or throughout the day, it is known as adrenal fatigue or burnout.
  • SNPs. A simple genetic test will help us understand other mutations (SNPs) that may be playing a role in your adrenal fatigue.

Urine tests:

  • Adrenaline (norepinephrine and epinephrine). This will give us more information about the state of your adrenal glands and methylation.
  • Organic Acids. This will help us evaluate your specific nutrient needs, antioxidant status, and to identify whether imbalanced bacteria or yeast need to be addressed.

IgA and IgG Food Panel:

  • Delayed Food Sensitivities to such foods as gluten and dairy.
  • When food sensitivities are present, it indicates Leaky Gut, which means that the cells lining your intestines are allowing undigested foods to leak through and trigger your immune system. This type of immune response causes inflammation and adrenal fatigue
  • Both food sensitivities and leaky gut can create adrenal fatigue, stress your adrenals and disrupt methylation.

Additional considerations:

If you have a history of infections, such as mono (EBV) or Lyme Disease, or toxicity from metals, mold, or other toxins, then we also need to evaluate whether they are still playing a role in the way you feel today.

Creating a Strategic Plan

Once you have your results back, we will be able to look at the pieces of the puzzle and see all the causes of your low energy. Then we can create a comprehensive, integrated plan that addresses each of the areas that need attention.

Since all these systems in your body are inter-related, it is as we help them work well together again that you’ll start to feel better.

If you are suffering from adrenal burnout, it’s always better to get your cortisol back to optimal first before addressing any other issues (such as MTHFR and methylation) because it dictates the function of your digestion, immune system, nervous system, and hormones. If you don’t have cortisol on your side, everything else will be more difficult.

We will also want to make diet changes based on food sensitivities, work to heal leaky gut and decrease inflammation, as well as to optimize your microbiome (bacteria living in your intestines). Once those steps have been accomplished, then we can add methylfolate and the other B vitamins, if more is needed.

I encourage you to work with a naturopathic doctor or functional practitioner who has specific training in this area. And I invite you to learn more about how to work with me one-on-one, so I can guide you through the approach I developed.

In fact, I decided to create a package that includes consultations with me and all of the important tests mentioned above. This way I can help you look at all the information and create a plan of action. I call it the MTHFR and Genetic Profiling Package. The idea is to simplify the approach for you so you don’t have to stress about the details—you’ll have me to guide you and all the benefits of a package, including discounts on supplements.

What Can I Do To Start Feeling Better?

  1. While awaiting results, you can start to support your energy levels by balancing your blood sugar levels. Balanced blood sugar throughout the day helps your adrenal glands to recover and your methylation cycle to function better. Eat balanced mini-meals every 3 or 4 hours through the day (if your blood sugar levels are varying a lot, you may even need to eat every 2 hours). Always combine a healthy carbohydrate, such as colorful fruits and vegetables or a gluten-free grain (such as quinoa, millet, and rice) with a protein like free-range poultry, wild fish, or organic nuts and a healthy fat (grapeseed oil, olive oil or fats in olives or avocados).
  2. Next, start supporting your adrenal glands and methylation cycle with nutrients.* B vitamins and electrolytes help both the adrenal glands and methylation, so starting with vitamin B1, B2, and B6 (P5P) plus magnesium bisglycinate either separately or as an electrolyte product get your body ready for methylfolate: A product called B-minus, for example, contains all the important B vitamins except methylfolate and methylB12. Another similar product is called Optimal Start, which includes adrenal-supportive herbs in it.Magnesium Plus contains magnesium with P5P. It can also help to have a multi-mineral product on hand as well to assist with the methylation pathways.

3. Once you are ready to start addressing MTHFR mutations and methylation, start slowly with 5MTHF and other methylation-supportive nutrients, and be willing to make changes as needed.

You could start by trying a very low dose of methylfolate (say 400 to 1000 mcg) once every three days. I recommend taking methylfolate WITH methylcobalamin (B12), because our bodies use them together. Here are two options: MethylGuard Plus and Liposomal Folate/B12.

It’s important to keep niacin nearby in case you experience headaches, irritability, anxiety, depression, joint pain, nausea, rashes, and/or heart palpitations as these could indicate that you’ve taken too much 5MTHF at one time and need help processing it.

4. Notice how you feel. It can seem counterintuitive to feel worse when taking methylfolate (5MTHF), even though it would seem that your body needs it. However, it can happen because if your body is not ready for more 5MTHF, it can overwhelm your body.

If you feel worse at any point, stop taking the methylfolate and contact a practitioner to assist you. This is why it is so important to work with a practitioner who can really listen to the way you feel and help you evaluate the more subtle imbalances that could be addressed with diet changes, nutrients and/or herbs.

5. Journal about your process. While you are taking addressing adrenal distress and methylation, it’s a good idea to monitor how you feel each day—perhaps with notes on your calendar or an app on your phone—this way you can tell whether a nutrient or dosage change is affecting you negatively.

Improving your energy once and for all

More than anything, I hope this article helps you to see that addressing methylation and adrenal distress is essential to improving your energy levels.

It is important to not overlook either of them, and instead it is imperative to address them both. You may not be able to support them at the exact same time but, over time, ensuring adequate methylation support while also optimizing your stress response, is likely to improve your energy levels and improve any other health concerns you have.

As someone with both MTHFR mutations and adrenal glands that need consistent support, I find that supporting them both is key to keeping my energy levels going all day.

For more about recovering from adrenal distress, please refer to my ebook, Dr. Doni’s A Guide to Adrenal Recovery, which you’ll receive when you sign up to receive my weekly e-newsletter.

Also be sure to check out the Stress Remedy 7 and 21 day programs, which allow you to start recovering from stress by changing your diet, getting better sleep, and starting to exercise. These programs are a great place to start to improve your energy level and get ready to address MTHFR and methylation.

–Dr Doni
29th April 2015

*Please keep in mind that any and all supplements—nutrients, herbs, enzymes, or other—should be used with caution. My recommendation is that you seek the care of a naturopathic doctor (with a doctorate degree from a federally-accredited program) and that you have a primary care physician or practitioner whom you can contact to help you with individual dosing and protocols. If you ever experience negative symptoms after taking a product, stop taking it immediately and contact your doctor right away.

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  1. Dear Dr Doni,

    You state that you have MTHFR mutations and adrenal glands that need consistent support but I was wondering if you are able to live a full and active life (e.g sport & fitness participation) with the appropriate supplementation? Or does this inhibit your activity level?


  2. one connection to sleepiness. Folate is necessary for melatonin production. When I started supplementing with folate, I found I had a circadian rhythm for the first time in my life. Needless to say, I have a lot of sleep to catch up on. Lack of sufficient melatonin cannot be good for your health.

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