Doctor Doni

How Adrenal Distress Affects MTHFR and Methylation

Dr. Doni Wilson discusses adrenal distress, how it affects methylation, and 5 tips for recovering – without prescription medication.

what is mthfr, MTHFR gene, MTHFR mutation, neurotransmitters, vitamin B12, folate, methylfolateMore and more, clients come to me with the knowledge that they have a mutation on the MTHFR gene, which is responsible for converting folic acid into folate to maintain optimal physical health.

Some have been told by mainstream doctors simply to take folate supplements, which they may have already started at a relatively high dose (10 to 15 mg per day). However, in my experience, addressing an MTHFR mutation is more complex than that.

The dose of methylfolate you might require is as unique as your body.

Moreover, other health issues may be slowing down methylation (the process by which folate and B12 are used in the body), and unless you understand and address those issues properly, taking folate may not lead to any significant improvement. It could even make you feel worse.

For that reason, my next few articles will discuss the various conditions that can bog down methylation and increase symptoms associated with an MTHFR mutation, to help you identify the ways you can improve methylation in your body.

Today, we’re going to look at adrenal stress – specifically:

What Are the Adrenal Glands?

Our adrenal glands are located just above our kidneys, one on each side of the body. While the adrenal glands have several jobs, one of the most significant is to help our bodies respond to and recover from stress.

The adrenal glands produce cortisol and adrenaline, hormones that prepare your body to respond to stress. Your heart speeds up, your muscles get ready to run, your mind focuses, and your blood sugar rises. Then, once the stress is over, cortisol and adrenaline levels drop back down, and your body returns its attention to things like digesting food, fighting infections, and resting.

The stress response is essential to our survival – but in the modern world, our bodies often hardly have a chance to recover before the next source of stress comes along. And for many people, the stress response never turns off, leading to anxiety, disrupted sleep, digestive issues, frequent infections, weight gain, and many other chronic health issues.

Too often patients tell me that their doctors have dismissed their symptoms saying “it is caused by stress.” To me, this is where we start. Helping you recover from stress is how I can help you return to feeling well.

How Much Cortisol and Adrenaline Should Your Adrenals Produce?

How much cortisol and adrenaline the adrenal glands produce varies from person to person – and bear in mind that these hormones are produced all the time, not just when we feel stressed.

So, the goal is not to have zero cortisol and adrenaline; that would make you feel very unwell. The goal is to have cortisol levels increase in the morning to help you wake up, and then to have cortisol levels decrease gradually throughout the day, to their lowest point during the night while you sleep.

When you are exposed to stress – anything that stimulates a bodily response, such as a shift in your digestion, your hormonal levels, your immune system or your nervous system – cortisol and adrenaline levels increase from your unique baseline. When the stress is over, cortisol and adrenaline return (again, these will be unique to your body).

What Is Adrenal Distress?

The way your body responds to stress is unique to you. It is determined partially by your genetics and partially by your exposure to stress earlier in life (and even your parents’ exposure to stress). I call this your “stress fingerprint.”

So, stress responses are not one-size-fits-all.” Some people may be more prone to producing more or less cortisol and adrenaline when exposed to stress than others – for example, if they have a COMT genetic SNP (single nucleotide polymorphism, i.e. a mutation). COMT is the enzyme that rids the body of adrenaline, while the SNP decreases the breakdown of adrenaline. Therefore, someone with such a mutation would experience increased adrenaline levels (when that gene is expressed).

Studies also indicate that almost 50% of children have had adverse childhood experiences (ACEs).1 As a result, those children are more likely to have elevated cortisol and adrenaline levels and, therefore, feel anxious and stressed throughout their lives.

Furthermore, your body can get stuck in stress mode,” meaning the adrenal glands don’t receive the signal to de-stress. In that case, they can become depleted, making them less able to respond to stress in a healthy way.

This is commonly referred to as “adrenal fatigue,” although not everyone experiences true adrenal fatigue, which is when both cortisol and adrenaline levels are low. In my experience, there are so many possible unique responses to stress that I prefer to use the term “adrenal distress” to describe any imbalance in cortisol and/or adrenaline production that is causing health issues.

What Are the Symptoms of Adrenal Distress?

The symptoms of adrenal distress vary from person to person and don’t necessarily correlate with how you feel. For instance, many people would assume that if you are tired, you likely have low cortisol levels, but that is not always the case.

We can’t guess whether your cortisol levels are high or low based on your symptoms; we need to test your levels to know for sure. And it is important to be certain, because your treatment will differ dependent upon what adjustments are needed.

Some of the most common symptoms of adrenal distress include:

Because cortisol influences your digestion, immune function, nervous system, and all the other hormones in your body, it is also common to experience:

How Adrenal Distress Affects the Methylation Process

As mentioned, methylation is the process by which folate and vitamin B12 are used in our bodies. I sometimes refer to methylation as the “B-vitamin cycle” because it is the biochemical process through which our bodies use B-vitamins to make SAM (S-adenosylmethionine – called SAMe, in supplements). SAM is then used in our bodies in many ways, including in the production of new healthy cells, in the breakdown of adrenaline, and in ridding the body of histamine.

Think for a minute about what happens when you are stressed. Your body makes more adrenaline to respond to the stress, but once the stress is over, your body needs extra SAM to get rid of the excess adrenaline. To make extra SAM requires methylation and B-vitamins. In this way, stress puts an extra load on your methylation system.

And I don’t just mean emotional or psychological stress. Stress in the form of environmental toxins, mold and/or metal exposure, and inflammation due to food sensitivities and leaky gut ALL slow down the methylation cycle, making it harder for the body to produce SAM.

In other words, when you are stressed and need more SAM, the stress itself slows down your ability to make SAM. That’s likely why we feel worse when stressed, and why so many health issues are associated with stress.

This is also why it is so important to address adrenal distress in order to achieve optimal methylation.

Why Taking Folate Can Sometimes Make You Feel Worse

As noted at the start of this article, mainstream doctors commonly address MTHFR mutations by prescribing folate supplements. However, if you’re suffering from adrenal distress, folate can sometimes make the problem worse.

Imagine you are stressed – whether it is due to a test you are about to take, relationship or financial problems, or eating foods and drinking alcohol that stress out your body, raising your blood sugar and causing inflammation. As your cortisol levels go out of balance, leaky gut worsens and the bacteria in your intestines can also imbalance, producing toxins that cause more trouble.

In this scenario, methylation is likely struggling under the stress, which means that if you simply start taking lots of folate, your body may be less able to use the folate effectively. As a result, instead of folate helping you feel better, it can cause headaches and anxiety.

That is why, as tempting as it can be to jump right in and take folate to treat your MTHFR mutation, it is much better to address your adrenal response first, and help your body recover from the effects of stress. Then, in many cases, methylation starts working better on its own, without even adding folate; or, if folate is needed, the necessary dose is much lower than when stress is blocking the methylation pathways.

5 Tips for Drug-Free Recovery from Adrenal Distress

In most cases, it is possible to recover from adrenal distress naturally, without taking prescription medications. However, working with an experienced naturopathic practitioner is essential to determining exactly how stress is affecting your adrenal response system, and which nutrients and herbs you need to correct your unique stress fingerprint.

Here are 5 tips I’ve learned after helping thousands of patients (and myself) recover from adrenal distress:

  1. Address your cortisol levels. If these levels are elevated, the first step is to use nutrients, herbs, and mindfulness techniques to address your stress response and get those levels closer to optimal.
  2. Match your doses to your unique cortisol pattern, e.g. if your cortisol increases after 7 pm, take nutrients and herbs that help decrease cortisol by about 6 pm.
  3. Know and address your adrenaline (norepinephrine and epinephrine) levels in addition to cortisol. If you only address cortisol, you’ll be missing part of the solution. If you do have elevated or depleted adrenaline, then knowing your genetic SNPs can be very helpful and addressing methylation will be essential to maintaining optimal levels long term.
  4. Always ensure that you have enough calming support before adding stimulation support. Even if you feel tired, if you add in support for low cortisol and/or adrenaline before you have enough calming neurotransmitters, like serotonin and GABA, then you risk feeling worse. Learn more about addressing neurotransmitters here.
  5. When ready to support cortisol and/or adrenaline, start slowly, and only increase to the dose that feels best to your body. My rule is: If you feel worse when you start taking a nutrient or herb (or medication, for that matter), it is best to stop and check in with your naturopathic doctor or practitioner.

The overall goal is to support your body to achieve optimal levels so that healthy signals will be sent out to the rest of your body, which can then help reciprocate the message, helping your body to achieve a renewed balanced state. At this point you’ll also be more resilient to stress in the future.

NOTE: If you have been diagnosed with Addison’s or Cushing’s Disease (extreme forms of adrenal distress), it is important that you follow the recommendations of your endocrinologist. You will likely need to take prescription medications, but you could work with a naturopathic doctor to determine whether you could additionally benefit from nutrients and herbs.

Closing Thoughts

I hope you found this article useful and informative. If you know anyone else who could benefit from this information, please feel free to share this article. To make sure you don’t miss out on future articles, please subscribe to this blog.

To find out if you may be suffering from adrenal distress, take my free online quiz. And if you’d like to learn more about adrenal distress and how to recover, you can get my 35-page eBook, A Guide to Adrenal Recovery: How to Go from Adrenal Distress to Optimum Health…Naturally for free, simply by signing up for my Weekly Wellness Wisdom newsletter. In that booklet, I’ll walk you through how to understand how stress is affecting your body and what you can do about it.

To learn how you can work one-on-one with me to help you address adrenal distress and MTHFR, click here to read about the consultation packages I offer. They all include testing for cortisol and adrenaline, my book, The Stress Remedy, the email tips from the 21-day Stress Remedy Program, and follow up appointments with me so I can guide you along the way.

I’d also like to invite YOU to attend a FREE webinar I’m giving on Tuesday, June 26th at 7 PM Eastern. I’ll be discuss stress, adrenal distress, how to check your cortisol and adrenaline levels, and how to recover – it’s what I call becoming a Stress Warrior. You too can learn how to be healthy even though you are exposed to stress, and even if you have MTHFR. Sign up here.

Finally, based on reader feedback, I created an online training where you can learn about how to address adrenal health and methylation. You can get that training for $47 here.

MTHFR Basics: The Answers You Need to Take Control of Your Health

This session is especially useful if you recently found out that you have an MTHFR mutation and you’d like to learn more about what that means. It’s natural to feel confused, overwhelmed, and worried about what this diagnosis means for you and your health, but there are answers. We’ll talk about my 5-step approach to optimizing methylation, and get you on track to take control of your health.

Learn more

As always, wellness wishes to you!

–Dr. Doni
14th September 2017


*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.



  1. Stevens JE. Nearly 35 million U.S. children have experienced one or more types of childhood trauma. ACES Too High News. 2013. Published 5/13/13, accessed 9/13/17.
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