How Your Brain And Nervous System Control Fatigue with Ashok Gupta

Content By: Ari Whitten

Are you experiencing “brain fatigue”? If you have either Chronic Fatigue Syndrome, Fibromyalgia, or you’ve been diagnosed with “adrenal issues,” you probably know that there are many experts who all have identified their own unique identification of the root cause. Some say the problem is the adrenals and cortisol, others say it’s infections or immune dysregulation, others say it’s inflammation and oxidative damage, others say it’s lymph problems, and others say it’s repressed emotions or psychological at its roots, and so on.

You might have tried an approach that targets one of these things in the past (maybe you’ve taken antioxidants or adrenal supplements or anti-inflammatory herbs, etc.), but you’ve probably noticed little or no long-term success.

Perhaps the reason why your attempts at fixing your fatigue haven’t yet been successful so far is that the real cause of fatigue is in your brain…

This week, I am talking to Ashok Gupta, who is one of the top chronic fatigue researchers. He’s done some groundbreaking research on the underlying cause of chronic fatigue, and he believes that the real root of fatigue isn’t the adrenals (as many people believe), but your brain. Specifically, the emotion, fear, and stress-processing circuits of the brain, a.k.a. the limbic system.

In this podcast, you’ll learn

  • Why chronic fatigue syndrome, fibromyalgia and “adrenal fatigue” all have the same root cause
  • How lots of different schools of thought are all myopically focused on one specific layer of dysfunction in the body as the “cause” of fatigue (e.g. the adrenals/cortisol, inflammation, immune system, sleep, lymph, psychology/emotions, etc.) and why they’re all just looking at a small slice of the overall pie without really understanding the true source of those dysfunctions
  • Why brain dysfunction — not inflammation, immune problems, or adrenal/cortisol issues — is the real root cause of fatigue.
  • How limbic system dysfunction causes fatigue
  • Why adrenal/HPA and cortisol issues are secondary to dysfunction in the limbic system of the brain. (Plus the “fatigue spectrum”).
  • What is limbic retraining and how does it work?

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How Your Brain And Nervous System Control Fatigue – Transcript

Ari Whitten: Hey there, this is Ari Whitten, and welcome back to The Energy Blueprint podcast. Today, I have a very special guest, who is one of the biggest researchers in the chronic fatigue syndrome space for the last 15 years. He’s published a number of papers and done a number of really groundbreaking studies in this field.

His name is Ashok Gupta, and he has developed a whole paradigm of chronic fatigue syndrome and related fatigue conditions that really revolves around the brain. It’s not, you know, an adrenal and cortisol and HPA access centric model of how these fatigue conditions developed. It’s really about the amygdala and the insula and some of these fear and stress processing systems of the brain as being the central, the key players in the whole condition.

He’s done some really groundbreaking work, like I said, and he’s actually tested this out. So it’s not just a theory, he’s actually tested it out with a number of different studies in people with chronic fatigue, and they’ve had really incredible results using some of these methods.

So, I had had a chance to actually speak with him on the phone a few days ago, on Skype. We had a call that was meant to be an introductory call and it ended up being like an hour and a half conversation of just really geeking out on the science in this area. It was just such a fun conversation, and I said ‘We need to do a podcast, and I need to have you on the show. I ideally want to do two episodes with you, because there’s just so much great stuff to share here.’ So, without any further ado, let’s get into the show.

Hi Ashok. Thank you for joining me. It’s a pleasure to have you on.

Ashok Gupta: Hi there Ari. I’m delighted to be with you here today. Thank you for inviting me.

Ari Whitten: Yeah. I just want to start off on a more personal note. We just met a few days ago, for everyone listening, and we had a little intro call just to talk things over and talk about my work, and talk about his work, and having him on the podcast and so on.

What was intended originally to be a five or 10 or 15-minute introduction call turned into an hour and a half conversation that was just such a fun dialogue, and brilliant conversation to geek out on, and the research in this area was just really fun. I just wanted to say I’m super excited to have you on, such a high level researcher in this field. It’s really an honor.

Ashok Gupta: Well, thank you. Thank you for that introduction. Yes, it was a really fun conversation, and I love talking about this stuff. I’m also quite a geek when it comes to researching and understanding this condition. It was a really stimulating conversation. You’ve got so much knowledge and so much to add to this area as well.

Ari Whitten: Thank you. I appreciate the kind words.

So, let’s talk about your background. What actually prompted you to get into this field and start studying chronic fatigue?

Ashok Gupta: I actually suffered from ME and chronic fatigue syndrome when I was at university. I remember those really difficult times, those moments when I literally had to crawl to the bathroom. It’s that feeling of ‘What is happening? Is my life over?’ Then you do some research. You speak to doctors and they say ‘Sorry, there’s no cure, you may have this for decades.’ Which is probably the worst thing you can say to someone when they’re experiencing that. It was a real low point in my life where I just said ‘What have I done to deserve this? I’ve just got this illness.’

It actually started after I had been to India. I developed some kind of virus, some kind of infection, and it affected my whole body. It took a long time for the infection to go, and even once the infection had gone, it never felt like it had gone. I felt that the illness just continued and got worse. Then I had to drop a year at university, and that was obviously a difficult time.

Like many people do, I did a lot of research into CFS and ME and fibromyalgia, trying to understand what causes these conditions. I specifically looked at the brain neurology of emotion. I’m very interested in brain neurology. At that time, in the mid-90s, it was still in its infancy to a certain extent. Not the way, how advanced scans are now. It was just really interesting to then come up with a hypothesis as to what causes the condition, from that hypothesis get myself fully well, and then I published a medical paper in 2002 which went through step by step the brain neurology and the background, and then I set up a clinic working with people.

In that moment, it was just beautiful. When you’re working with people who’ve had this condition for years and decades, and suddenly they see light at the end of the tunnel, suddenly they see there is a way of getting better, and then they improve, and then they get their lives back. I live for that.

That, for me, is just a beautiful moment. Not just for the feeling of ‘I’ve helped someone,’ but just in that moment to see that sheer gratitude that people have in their eyes, and the gratitude you have for doing this kind of work, it’s priceless. That’s what keeps me going. It’s a reason to get people better from what is a huge amount of suffering that people go through.

Ari Whitten: Yeah, I completely agree. Actually, just before I got on this interview with you I saw a message in my members Facebook group of a woman saying … Just supplying this one technique I teach in the program. She was saying her migraine frequency has gone from nine a month to one in the matter of a few weeks, and it was just … You’ve just made me think of that because it brings such a smile to my face to see things like that. Like you said, that’s why we do what we do, so I really resonate with that.

What ME, CFS, and related syndromes are, and how they are related. 

So, let’s talk about some of these different conditions. You mentioned ME, which is myalgic encephalomyelitis. That’s an unfamiliar term for most Americans. I know that’s more common to hear I think maybe just in the UK or maybe in other places in Europe. There’s a number of related conditions here. CFS, ME, kind of synonymous, then fibromyalgia, and then multiple chemical sensitivity. I would love if you could just talk about some of those.

We could also talk about some of these other things, like adrenal fatigue, and HPA access dysfunction, and burnout syndrome. There’s all these other names, but I think CFS, fibro, multiple chemical sensitivity … It would be great to clear things up there.

Ashok Gupta: Yes. You know, a lot of these conditions have what we call an arbitrary diagnosis in the sense of ‘Here’s a list of symptoms: do you have five of these or three of these or two of these?’

What we’re doing is we’re fitting patients into a box, saying ‘Right, according to this tick list, you fit into this box. According to this tick list you fit into this box.’ Actually, all of these conditions are related and have the same underlying cause, in my humble view. It’s a spectrum of different conditions with an emphasis on a particular area.

ME and chronic fatigue syndrome: the emphasis is on fatigue and some immune symptoms. That tends to be what differentiates it. Fibromyalgia, there’s more of an emphasis on pain. Chemical sensitivity: that is a bit more different. That’s more an emphasis on, obviously, sensitivity to chemicals and mold and things like that. Then we have electrical sensitivities where people become highly sensitive to electrical fields and mobile phone radiation. Then there’s even irritable bowel syndrome, which is very common in the population, where people have symptoms predominantly in the stomach.

I believe that all of these different conditions, they’re very similar and have so many cross overs because there’s a similar underlying cause. Many people with ME and chronic fatigue syndrome will have pain. Many people with fibromyalgia will have chemical sensitivities, because the underlying neurology is very similar.

I term all of these conditions neuro immune conditioned syndromes, or NICS, N-I-C-S, because the neurology is essentially involved, we know that. Well, we know that as a root cause, but that’s my view. Immune, because in most of these conditions aspects of the immune system are involved. Conditioned, because I believe the system has got into the habit of responding based on a previous experience, and a syndrome because there’s not one specific set of symptoms you can say that every patient has. There’s a whole bunch of symptoms together.

I think that when we start talking about neuro immune conditioned syndromes, it helps people feel that there’s … Not a justification, but there’s an understanding of what’s actually causing the condition, rather than thinking it’s psychosomatic in any way. I would have that title for all of those conditions.

Ari Whitten: Excellent. One of the things you and I chatted a bit over the phone when we spoke the other day, which I really resonated with and I really enjoyed, was this idea of all these different schools of thought. Everyone kind of myopically zeroing in on one particular thing that they think is the thing, so it’s the inflammation, or it’s the oxidative stress, or it’s ‘We found sleep problems in people with CSF,’ it’s the sleep, it’s a gut issue, it’s a HPA access issue, it’s this, it’s that …

What lead Ashok to conclude the brain is the primary cause of fatigue 

There’s all these different kinds of camps, all these different schools. What led you to the conclusion that the primary source of the dysfunction is in the brain?

Ashok Gupta: Well, just like yourself I’ve had a similar experience where I present at the ME CFS Conference, which is held every couple of years. In the room you have every single representation of medicine that’s present. Each of them has found an abnormality, and one says ‘Aha! We’ve found the root cause because we’ve found this physical abnormality.’ They’ll go up and they’ll present, and everyone will be like ‘Wow, yes, maybe that’s the cause.’ Then someone else will come and present and say ‘Well, we found this, and we found this.’

You suddenly realize that it can’t be that … They can’t all be right in terms of a root cause, but they can all be right in terms of those observations. What is it that effects the entire system? The nervous system. So, the nervous system in some ways is like the software of the body. It’s runs the hardware. The central nervous system is that software and the brain is the head of that software, which makes sense.

I do believe that whilst there are local effects, the programming, the software, is what’s going wrong, and the software, predominantly, sits in the brain. That then makes sense to me. When the brain is malfunctioning and not keeping the body in homeostasis, or balance, when it goes out of balance, that will affect every single cell, organ, and system in the body. Therefore there can be a very obvious centralized way that this could be occurring.

Ari Whitten: Yeah. I want to give people a little visual to understand what we’re talking about because people who are not already science geeks may have a bit of difficulty grasping this concept, how there could be multiple layers of dysfunction occurring simultaneously, and why it’s so important not to zero in on the wrong one, or one that is not an essential cause.

Imagine, just as a quick, simple visual, imagine a stream. At the top of the stream someone is pouring all kinds of pollutants and radioactive stuff into the stream, but downstream people are eating fish out of the river, eating plants out of the river, and getting sick from it. So we think ‘Oh, it’s the plant that’s the problem,’ or ‘Oh, this fish has a certain toxin in it and therefore the fish is the problem.’ For everyone listening, I’m just trying to illustrate upstream versus downstream effects. There’s some kind of more upstream thing that’s going on, and then there might be other layers of dysfunction that occur later on as a result of that underlying root cause.

What Ashok is saying is basically that what he believes based on this evidence is that the brain is really the central player and then there are many other layers of dysfunction that occur in the body as a result of that dysfunction. Is that pretty accurate?

Ashok Gupta: Yes. And not only that, there can be secondary conditions which occur. Let’s say, eating those fish downstream may then cause another secondary effect, a kind of condition of its own, which then complicates the situation.

As an example, if we’ve got a compromised immune system upstream, so that’s your equivalent of pouring the poisons down the stream, if we’ve got a compromised immune system upstream, downstream that means that we’re then going to have high viral titers. We’re going to have higher loads of opportunistic viruses and bacteria in the body, and those opportunistic viruses and infections will cause further downstream effects. That’s when then researchers say ‘Aha! We’ve found X percent of patients have too many of these viruses and bacteria, therefore that’s the cause and that’s the reason for the condition.’

Ari Whitten: Right. If I could just add one thing: I think it’s a shame, personally, that so many people are locked into that kind of reductionist, myopic view where they’re looking for the one biochemical abnormality and they’re not looking at things holistically. Like what you’re talking about: how this is a big picture, how vicious cycles can be created through some of these downstream dysfunctions now create their own vicious cycle and lead to more dysfunction.

Ashok Gupta: Yes. Yes, absolutely. I think it was something that you mentioned about when you were studying medicine, I think you mentioned an example of diabetes where they’re talking about diabetes but there’s no mention of diet and activity as a way of improving it. In the same way, I think that we’re only going to solve these NICS, these neuro immune conditioned syndromes, when we we recognize that there’s something wrong with the software and a more holistic vision is required, rather than honing in on one particular thing that’s wrong, finding a drug that will then treat that one particular thing.

If we find a miracle drug that cures all of these conditions, brilliant. I’m out of a job, and I would love to get everyone better, but I don’t think that’s ever going to happen because of the nature of … They’re software conditions, not hardware conditions. The software’s gone wrong, which then makes it look as if the hardware’s malfunctioning.

Ari Whitten: On that note, I think so much of the line of thinking and research that goes on in the pharmaceutical industry is basically that. It’s looking for the one biochemical abnormality in so-and-so disease, and then ‘How can we find a drug to interrupt that biochemical pathway?’ With the idea that that’s going to lead to a cure. Outside of infections, acute, life threatening infections, I think that paradigm and that approach has been a pretty massive failure when it comes to chronic conditions. I think, going back to that visual of the stream, it’s not about interrupting how the toxin gets into the plant or the toxin gets into the fish, it’s about going to the top of the stream and stopping that person from pouring toxins into the river in the first place.

Ashok Gupta: Exactly.

What the main causes of CFS are 

Ari Whitten: So, when it comes to CFS, what are the main causes? What does this actually look like in terms of … I know on your website you have a nice visual of underlying predisposing factors, then some of the main triggers for the condition. Can you kind of just take us through what this whole process, what this whole sequence of events looks like, and what it manifests in?

Ashok Gupta: Yes, absolutely. I’ll lead with this analogy, which I think will kind of help. Before I look at the analogy, I’ll talk about those predisposing factors.

So, we know there could be some genetic factors that make it more risky for someone to get a neuro immune conditioned syndrome like CFS, like fibromyalgia. That’s often combined with chronic or acute stress, combined with some kind of illness. We’ve got three factors: some genetic factors, perhaps some factors around upbringing, then we’ve got the physical trigger, so the illness, and then chronic or acute stress. Most people do recall a period of chronic or acute stress in the run up to getting the condition.

I’d like to give the analogy of: let’s say your body is a castle, and you are the king of the castle. The conscious mind is the king of the castle, and your body is the castle. The army and the navy are like the immune system and the nervous system. Let’s say the army is the nervous system, and the navy are the immune system. They’re there to defend the castle.

If that castle is under a lot of stress, let’s say there’s been a bad harvest, let’s say, or they’ve already fought some wars recently, the whole castle is exhausted. The army and the navy are exhausted. That’s equivalent to the chronic stress that people are experiencing at the beginning of the condition. All of the immune system and the nervous system are not functioning correctly. There’s exhaustion in the system.

One of the reasons that exhaustion is happening is because the army and navy have been fighting all these battles, and because they’re exhausted, the next virus or bacteria comes over the hill, so the next invading army comes over the hill, and the army and the navy, they’re so exhausted, they’re fighting and they’re fighting, it’s taking them ages to defend the castle. Normally, they would have fought off those invaders within a week. Now it’s taking months, weeks and weeks, months and months, to fight off these invaders.

Eventually, the body, the army and the navy, have fought off that invading army. But the whole castle is exhausted, thinking ‘We just can’t handle any moreof this.’ The army and the navy become so traumatized by the experience they’ve gone through because survival is the most important thing. They’re thinking ‘If we don’t defend against another invading army, we’re going to lose the castle. Everyone’s going to die.’

Then, to err on the side of caution, when they simply notice anybody coming over the hill, they massively trigger the nervous system and the immune system. The army and navy suddenly send battalions over the hill just at the even mere suggestion that they may be under threat. Then what happens is simply the fact that the whole castle is exhausted, those signals from the body become a trigger to the brain that we’re still in survival mode, we’re still in danger, we’re still under threat.

The brain detects the signals from the body, the signals from the castle, think ‘Uh oh, we’re still in danger. Survival is paramount and we’re still in danger. Let’s trigger the army and the navy. Let’s trigger the immune system and the nervous system.’ Then the brain triggers those systems continually, which then creates the symptoms in the body, and those symptoms in the body circle back to the brain again. The brain thinks ‘Oh no, we’re feeling exhausted, we’ve got even more symptoms, we will not be able to survive another attack. Quick, trigger more immune system, more nervous system.’ We get caught in a vicious cycle where the brain is over triggering defensive systems which is causing the very issue it’s trying to defend against. The brain gets stuck in a loop, essentially.

What’s interesting is every year … We talk about flu: every year thousands of people, hundreds of thousands of people die of flu when they have weakened immune systems. Many people report that when they first got ME or chronic fatigue syndrome it was after some kind of flu-like illness. That shows us that the body can go into hyper-defense mode as the result of a flu virus because it is life-threatening to us. It becomes then that self-fulfilling prophecy in terms of: the brain anticipates danger, and is creating the very danger that it’s sensitive to, until eventually, the whole system becomes so exhausted that there’s adaptation in receptors, the HPA axis is no longer responding, and when we have to do an activity the system is just downgraded completely because it’s so used to the overstimulation.

We’ve used up those hormones and those transmitters that normally make us feel good. We’ve got low serotonin, dopamine, oxytocin, adrenaline, noradrenaline … The whole system is exhausted, and therefore we can no longer respond to stress and to activity.

Ari Whitten: It’s interesting. There are so many different layers of dysfunction going on. There are studies, as we talked about the other day, there are studies about different biomarkers in chronic fatigue. You might look at inflammatory cytokines as a potential biomarker. You might look at HPA axis dysfunction and morning cortisol or diurnal cortisol curves during the day and how that relates to chronic fatigue, or oxidative stress going on in the cell or the blood or something like that. All these people looking at those pieces of the puzzle, and maybe even identifying certain abnormalities in certain cases.

Why Ashok has identified the brain to be the crux of fatigue 

Why do you think it’s the brain, specifically that’s the crux of it all?

Ashok Gupta: As mentioned, because every peripheral system is affected so powerfully, there must be a centralized mechanism that is causing this. On top of that, we know that in CFS and fibromyalgia … The CFS community is now catching up with the fibro community in terms of brain research. We already know that there are profound changes in the brain.

We know there’s reduced volume in the prefrontal cortex of patients. We know that the insular shrinks. The insular is the part of the brain that essentially takes in all incoming information from the body and creates an appropriate autonomic response and an appropriate immune response. We know that part shrinks and becomes hyperactive as if it can’t handle all the incoming data and is overstimulating the brain. From some EEG research we know that the brain goes into hibernation mode where it literally … It’s so obvious why people can’t think clearly or can’t recall and their memory is poor. It’s because the whole brain is almost shut down. It’s almost in delta wave sleep mode because of the overstimulation and the exhaustion.

So there’s so many physical abnormalities and brain abnormalities. We also get inflammation in the body, inflammation in the brain. I believe that this is in the brain simply because after that traumatic event, so the traumatic event is the physical illness and the chronic stress, a legacy is left from that interaction. The brain, as the kind of superior part of our bodies that keeps us safe, ensures our survival, is also the head of the immune system as more and more research is showing. Therefore, to me, it’s the most likely candidate for this.

How the brain has a role in classic symptoms of chronic fatigue 

Ari Whitten: Great. I know you’ve talked about … You just mentioned some of the inflammatory or immune abnormalities, but there are also explanations for how the brain can affect some of these other symptoms, how the brain has a role in some of the classic symptoms of chronic fatigue: post-exertional malaise, muscle pain and muscle dysfunction, even gut issues, irritable bowel, and so on. Can you talk a bit about how the brain relates to some of those symptoms, or how dysfunction in the brain plays a role in creating some of these symptoms?

Ashok Gupta: Yes. I spend a lot of time researching every single symptom and how it can be related to immune and nervous system dysfunction. The immune markers, they are simply occurring because there’s overstimulation of the immune system and dysfunction of that immune system. You’ll get some markers which will go up, some markers which go down, because the immune system just isn’t designed to be stimulated continually, continually in the background.

Then in terms of, let’s say, muscles, muscle pain, et cetera: when the nervous system tightens all the muscle groups you’ve got a build-up of lactic acid which causes pain, which causes fatigue. If we’re talking about the stomach and the gut, we know from studies on people with severe anxiety and depressive syndromes that actually they also have similar patterns of gut dysfunction.

People talk about leaky gut, they talk about an incorrect balance of good and bad bacteria in the gut, irritable bowel … That’s simply because when we’re in fight or flight mode, or in danger mode, defense mode, the gut shuts down. It doesn’t function correctly. When the gut shuts down, you’re putting food through it, it’s not being digested correctly. The bacteria balance is just incorrect. The muscle groups tighten, and therefore we have diarrhea or constipation or both, oscillating between the two.

The gut issues once again can be explained by an overactive sympathetic nervous system. Every symptom that I see can be explained … Pain: once again, we know with fibromyalgia, if you keep muscle groups tightened for days and days and days with no parasympathetic activity, so no healing of the muscles, then you are going to get immense amounts of pain build up. You’re also going to mean that the peripheral nerves become highly sensitive. They’re sending more pain signals to the brain, and the brain magnifies those pain signals as well and sends localized inflammation back to the muscles to deal with whatever is causing the pain.

Ari Whitten: Right. I know there’s quite a bit of research on central sensitization related to fibromyalgia and muscle pain.

Ashok Gupta: Absolutely. The two systems are working together. Central sensitization, which is causing peripheral pain, but also central nervous- the immune system is causing local inflammation which is contributing even further to that pain. Do you can see the vicious cycle that goes on in fibromyalgia.

Post-exertional malaise: people who go to the gym, they’ll know that straight after you go to the gym, you don’t feel the pain straight away, but you tend to feel it 24 to 48 hours later. What’s happening there is, in my view, when we’ve stretched our muscles, when we’ve used our muscles, the body goes into parasympathetic mode to repair the delicate muscle fibers, and also expand them if we’ve used a particular muscle.

In the case of ME, CFS, and fibro, and these conditions, there’s not much parasympathetic activity. So 24 to 48 hours later, instead of that nice feeling of a slight ache, but it’s being healed and repaired, instead you get a huge amount of pain, a huge amount of fatigue. That repair, heal, and digest system has not kicked in 24 to 48 hours later, which normally happens when you are exercising.

Ari Whitten: Yeah. I think the classic symptom, to go on a very basic level, the classic symptom that we’re really talking about here is fatigue. Fatigue itself is a symptom. One of the things you said in the conversation the other day was that if we didn’t …

Why fatigue is a protective symptom

Fatigue is a protective symptom. In a way, it protects us from ourselves. You talked about the type A personalities, and why fatigue is so protective. I would love if you could just repeat a little bit for everyone listening on why that is, why fatigue is protective for some of these people.

Ashok Gupta: Yes. Imagine you get flu. Imagine you had the flu virus but you felt no fatigue, no exhaustion. You would probably continue on your day as normal, and you’d actually be putting your whole life at threat, at risk. Our immune systems have evolved, over millennia, to force us to be tired, exhausted, headachy, lie in bed and do nothing so we are not using up that precious energy doing other activities that is channeled to healing.

That’s where the word patients come from. The word patient comes from being patient, resting. Most conditions actually go through patience, through not overexerting oneself and allowing one’s body to do the healing. In the same way, fatigue is a protective mechanism. Now, when it comes to these conditions, that fatigue, often people don’t listen to that fatigue. They overexert themselves. They push through. I believe that’s not going to help. Pacing is a very, very important part of this condition.

We don’t say there’s one particular personality type that gets these kinds of conditions, but we do notice that there is a preponderance towards not necessarily type A, but achievers, helpers, and approval seekers. This are people where, if we have one of these traits … Achiever is my sense of self, relies on achievement. Helpers put other peoples’ needs first, so their sense of self, relies on helping others and being there for others at their own expense. Approval seekers, people pleasers, they tend to be people who won’t express how they feel but instead are always worried what other people think of them and ‘Are people judging me?’

The whole population has those to a certain extent, but we find that people who get these conditions tend to have more of that. The reason that’s interesting is because we know that people who have these traits have a background increased level of amygdala stimulation, amygdala being the fight or flight response from the brain. We also know that they have more fatigue in life in general, and more exhaustion and are more prone to anxiety.

Often, at the beginning of the condition, they don’t take those signals of fatigue seriously. They push through, and they push through. Talk to most clients, they’ll say ‘I pushed through at the beginning.’ It could be that some of those very subtle personality traits mean that they try to push through and never relax, which then means that their immune system and nervous system goes into that traumatic phase of overstimulation, which then means that the body stays in this altered state. Even when they have this condition, they often find it difficult to pace themselves.

A big learning of getting better is not only changing the first vicious cycle, or the loop in the brain that I spoke about, about training the brain to not be so sensitive to signals in the body, but the second cycle that we’re retraining is getting people relax the nervous system at an overall level and a deep acceptance of the condition being here, so that they can enable a deeper level of healing, otherwise how can a parasympathetic nervous system heal us if we have one of these traits where we’re thinking ‘I’m ill, I can’t achieve, I can’t help others, I wonder what people are thinking of me, how are they judging me?’ All of this is just creating more stress and pressure.

How adrenal fatigue figures into what Ashok is teaching 

Ari Whitten: Yeah. Okay, beautiful. Let’s talk about one of my favorite subjects, something we talked about the other day, which I found your take on fascinating: adrenal fatigue and HPA axis dysfunction, the roles of adrenals and cortisol in all of this. Where does adrenal fatigue, this concept of adrenal fatigue, where does it figure into everything you’ve been talking about as far a chronic fatigue and fibro and some of these other conditions that are accepted within the mainstream medical community.

Quick side note, for those of you who are unaware: adrenal fatigue is not an accepted condition within the conventional medical community. It’s purely an alternative diagnosis. You can Google many articles online, from doctors who are endocrinologists who are basically saying adrenal fatigue is nonsense, it doesn’t exist. But where does this concept that the alternative medical community is talking about, where does that fit into this picture? How does it relate to some of these other fatigue conditions?

Ashok Gupta: Okay. When we encounter a danger, and that danger could be a five o clock deadline, an argument with your partner, stress, dealing with your kids, whatever is the source of that stress, there are different parts of the brain that first respond.

The prefrontal cortex and the amygdala, our danger center and the limbic system, the emotional brain, those particular structures create communication in the brain in terms of what is the appropriate response. The amygdala then sends messages onto the HPA axis, onto the hypothalamus, the pituitary, and then the adrenal glands.

The hypothalamus is often quoted as the centerpiece of our autonomic or stress reactions, but actually, it’s just a slave of what the rest of the brain thinks it should do. It’s more a discussion between the prefrontal cortex and the amygdala. It’s like a game of tennis that goes on.

Ari Whitten: Let me just quickly interject something. I want to emphasize that point because it’s so important. There are so many people out there talking about the adrenals, about cortisol, even to go one step more upstream, about the HPA axis. Like you said, the hypothalamus and the pituitary, as the centerpieces, as the origin, as the most upstream thing …

So many people trying to explain fatigue through that model. It’s cortisol, it’s the HPA axis.

I just want to emphasize what you just said to everyone listening, which is the HPA is not the origin. It is the slave of these other structures in the brain. I really want everyone listening to get that distinction. It’s really critical. The HPA axis is not the most upstream thing. It is the slave of the amygdala and some of these other centers in the brain.

Ashok Gupta: Yeah. I’ll give an example of that. Surveys- They asked people in surveys ‘What’s the biggest fear you have?’ Most people think their biggest fear is death, but actually, the biggest fear the population has is public speaking. So when we’re public speaking the amygdala, and they found this, is reacting to the environment and thinking we’re in danger. Other brain structures are involved, it’s not just the amygdala. Those signals go up to the prefrontal cortex, and the prefrontal cortex, our conscious mind, has to make a decision as to whether we should fight, so ‘Yes, let’s go for it, let’s do this,’ or do we run away flight.

Those signals are then sent back to the amygdala, in terms of the appropriate response, together with … The prefrontal cortex also has connections back to all these other brain structures. There’s a collective decision in the conscious and unconscious part of the mind: ‘What should we do now?’ If it’s very unconscious then the amygdala will send signals directly to the hypothalamus: ‘Right, trigger the fight or flight response via the HPA axis, trigger cortisol, trigger adrenaline.

Those systems then get overstimulated. At some point, the adrenal exhaustion, or adrenal fatigue, is simply when that system can no longer give the body the resources to respond.

It’s obvious. If you keep flogging a horse to run, and to run, and to run, eventually that horse is going to get exhausted and has run out of the resources, whether they be the resources of the actual hormones themselves or neurotransmitters, and it takes time for that to replenish. If we never stop hitting that horse, any little bit of replenishment gets used up straight away. It’s like we’re flogging a dead horse. We’re trying to get energy out of the system that has not had time to heal itself and to rest.

A lot of burnouts, traditional psychiatric or psychological conditions like burnout, go through an adrenal exhaustion phase, where a person feels so anxious they no longer have the energy or the motivation to be able to do things. What they need to do is go off on an island somewhere and rest it off. They can then heal their system and get back to normal.

The issue comes when the adrenal fatigue continues because of the vicious cycle that we’ve spoken about. The difference between burnout and these conditions that we’re talking about is that in burnout there’s still an opportunity for someone to rest, heal the system, and replenish.

In the case of neuroimmune conditioned syndromes, the brain has now become conditioned to respond to that lack of energy, to that lack of resources, to the adrenal fatigue, which then means that the symptoms create a vicious cycle of reaction and never allow the adrenals to go back to their balanced state.

Some people will say ‘Oh, hang on Ashok, your hypothesis means we should find loads of cortisol, loads of adrenalin, loads of noradrenaline in the system.’ Of course, there’s no fixed pattern. The reason there’s no fixed pattern is each person when you’re taking the urine sample, you don’t know where they are in the cycle. Have they replenished their system? Have they replenished, had some rest, then overstimulated the system to cause more stress hormones in the body? It’s a mixed picture.

What we do know in CFS is that that HPA axis is downgraded, so it’s no longer able to give us the resources that we want because every system in the body attempts to achieve balance. If you’re overstimulating it, it will downgrade its responses.

Ari Whitten: On that point, as we talked about the other day, I’ve done a really deep dive into the literature around adrenal and HPA axis function as it relates to burnout, to chronic fatigue syndrome, to every other fatigue syndrome, there’s a number of different names for it in literature.

One of the things that’s interesting that lines up with what you’re talking about, is yes, some studies detect hypoactive HPA axis function or depressed HPA axis function, but there’s a number of studies that have found that it’s only detectable deep into the course of severe illness. In other words, it is not present at the early stages, or the onset of that condition.

What that means, for everyone listening, is you can’t claim it’s the cause unless it is detectable around the onset or early stages. If it’s only present deep into the course of illness, in the most severe cases that have gone on for a long period of time, that’s something that’s clearly a downstream effect, not an upstream affect.

Just wanted to mention that. The research really supports the idea that yes, it can occur, but it’s quite clearly a downstream effect of some of the other things that you’re talking about.

Ashok Gupta: I’m really fascinated by the research you’ve been doing. Well done to put all of that together. It’s a thankless task.

Ari Whitten: It is.

Ashok Gupta: But hopefully now that you’ve done it people will take notice and realize this is incredibly important research that you’ve put together. So thank you for that.

Ari Whitten: Thank you. There’s been a number of other literature reviews on more narrow topics, but this will hopefully be the most comprehensive review of all the studies that’s been put out there. I actually just finished going through the last few studies yesterday, so it’s getting pretty close to putting it all out there.

The spectrum of fatigue and where adrenal fatigue fits in

On the subject of adrenal fatigue, you and I talked the other day about a kind of spectrum to understand where adrenal fatigue fits on this spectrum of fatigue. Could you kind of explain that concept?

Ashok Gupta: Yes. In the entire population, I see it as a spectrum. We live in a society, a modern society, which has a pro-inflammatory bias. Now what that means is because of our diet, because of our stress levels, because of pollution, in both the environment and our food, our system is predisposed to get triggered, in terms of the immune system response. If you look at a lot of the population they often complain about fatigue, insomnia, these kinds of generalized background symptoms, because of the lifestyle that we have.

My background’s Indian. When I go to India, you go to these villages in the middle of nowhere, and they don’t have access to healthcare, they don’t have the modern amenities that we have, and yet they’re happy, they’re healthy. They don’t have access to a doctor, but they don’t have these symptoms of fatigue or anything like that. I’m thinking ‘What’s going on here? It doesn’t make any sense.’

Then you realize that they live in close-knit communities. They don’t have huge expectations of life and what they expect to get from it. They eat generally organic diets, which are lots of freshly cooked food, lots of spices, and there’s a lot of vitamin D available, a lot of sunlight. I’m just thinking ‘How can it be that they seem so much healthier and happier than we are with all the amenities and all the modern things?’ It’s because modern life gives us that pro-inflammatory bias, which also increases levels of anxiety and depression.

The general population is probably in that area, then there are people who overstimulate their system through too much stress and anxiety, which then gives them … They move into the spectrum of adrenal fatigue. They’re still able to involve themselves in life, but it’s a grind. They’re spending evenings and weekends exhausted and trying to sleep it off, but they haven’t moved into chronic illness yet.

The moment that they then, that their systems, their brain starts detecting the adrenal fatigue as an issue itself, something to be anxious about, something that indicates a lack of homeostasis and potentially a threat to survival, then we move into the chronic fatigue state. A cycle has begun to happen and we’ve got chronic fatigue.

Then we move into chronic fatigue syndrome, that lasts for more than six months. The neurological learning has now become very deep. The brain has learned that any signal in the body represents danger to survival, and therefore we must keep the whole mind and body in a state of readiness and alert, by triggering the nervous system and the immune system. So then you’ve come into a vicious cycle. You’re now into chronic fatigue syndrome.

Then you move into the areas of ME, or severe fibromyalgia, where the vicious cycle has become so vicious and so fast that someone can move to being bedbound. What we also notice in these conditions, which helps me feel it is a vicious cycle, for those of you who are mathematicians or physicists, the illness tends to be quite up and down. If you as people they have good days and bad days.

Now, if there was something wrong with the hardware … If you break your leg, you break your leg. If you have cancer, you have cancer. It’s a purely organical shift in the physical hardware would mean that you’re pretty much the same every day. But in this situation, you have ups and downs. Good days, bad days, good weeks, bad weeks. We know that cycles can only occur if there’s a feedback looping the system.

Therefore, I believe that the software is where the issue is which is causing this vicious cycle, which then means we have up and down days. That’s when we get to the severe, severe illness, bedbound, almost paralyzed, is when that vicious cycle has become so automatic that it bypasses conscious awareness completely and the system is in a complete terrified state of survival mode.

Rather than seeing these conditions as something’s gone wrong in the body, or something bad has happened, we can actually see it as an evolutionary protective defense mechanism that is erring on the side of caution. It’s overprotecting. We see this quite often in so many different conditions. I give the example of a phobia. The system is overprotecting. So if you’re afraid of flying, the body’s thinking going into this metal box and flying at 500 miles an hour is not a safe thing to do, therefore I’m going to create a phobic response to defend this person and ensure survival. It’s an over-response. It’s not logical, but it’s an evolutionary advantageous thing for that person to do.

Ari Whitten: Yeah. Beautiful explanation. One of the things that I think is particularly worth noting about this is most people do not talk about the relationship of ”adrenal fatigue”, or burnout syndrome, in relationship to chronic fatigue syndrome.

If you even … I’ve looked online and there’s almost no one even attempting to talk about it. Basically, right now, we have different groups of people using different words to describe what I guess on the surface are different conditions. If you go to the mainstream medical community they’ll talk in terms of chronic fatigue syndrome, or ME, or fibromyalgia, and they don’t recognize any concept of adrenal fatigue or HPA axis dysfunction as being a primary source of this fatigue. Then if you go more into the world of naturopaths, alternative medicine, they talk in terms of adrenal fatigue. ‘Do you have adrenal fatigue or not?’ People are using these different words.

What I love is the way you’ve mapped this all out on a spectrum, and potentially some of these things that might be labeled adrenal fatigue or burnout syndrome or something like that might be early stages on a progression towards something, more serious chronic fatigue.

How hypothyroidism can be a symptom of chronic fatigue

Ashok Gupta: Yes. Chronic fatigue syndrome and fibromyalgia, I would class them as having adrenal fatigue as one symptom. Potentially also hypothyroidism. I presented, recently, at the Thyroid Conference in the UK. I’m looking at the symptoms of people with chronic thyroid problems and the symptom list is very similar to chronic fatigue syndrome. So, the chicken and the egg: which came first? What’s causing what?

Ari Whitten: Exactly.

Ashok Gupta: It’s very difficult to say. A lot of crossovers.

Ari Whitten: On that point, one of the interesting things that we talked about the other day is that there’s some research now indicating that fatigue is in a way almost like a hibernatory response. Especially severe, chronic fatigue. It’s a similar metabolic state to hibernation.

A researcher at UCSD named Robert Naviaux has mapped out what’s called the metabolomics of this, measured all these different blood markers, over 600 blood markers, and found that it’s a similar kind of downgrading of the overall metabolism to what might be expected, almost in a hibernation-like state.

On that point, if you’re getting this overall downgrading of the metabolism as a protective mechanism – you mentioned thyroid hormones and hypothyroidism. Thyroid hormones are a main controller of the metabolism, so what you would expect to see in a scenario where the body’s having this kind of reaction, is you would expect to see one of the things that would be downgraded would be thyroid hormones, as part of this protective mechanism of the body.

The question is, like you said, chicken or the egg? Someone might look at a blood test and say ‘Oh, you have the symptoms because your thyroid hormones are low,’ whereas another person might look at it and say ‘Well, of course, thyroid hormones are low because your brain’s behaving in this way, there’s this overall protective mechanism that the body’s engaging and the body is intentionally downgrading thyroid response. There’s definitely some chicken and egg arguments going on there.

How the brain is in hibernation mode in CFS patients

Ashok Gupta: Yeah. For me, once again, it’s a cycle. There’s some great work done by Dr. Marcie Zinn and Dr. Mark Zinn on EEG on ME and CFS patients. They found that the brain is in hibernation mode. It’s in this kind of delta wave sleep mode. Their research is very interesting because it’s the closest you’ve ever seen to clustering. They map the patients and they’ve got the healthy cluster and the CFS cluster. In most research, you never see definitive clusters, but in their research, it’s very. Very definitive and very, very to see.

Once again, it could be a symptom, but in my view, it’s … Well, it is a symptom. It’s part of that protection mechanism where the whole body is going into a survival state because it thinks it’s in danger. When you overstimulate the brain, the brain eventually runs out of those neurotransmitters and those resources, and once again, downgrades its function.

People experience that, right? If you have a really difficult day, a really stressful day, in the evenings, although you’ve not moved, you’ve not run a marathon, you’ve just sat at your desk all day, but you’ve had a really stressful day, you come home, what do you want to do? You just want to switch off your brain, right? You want to just watch some mindless TV or go for a walk or chat to your friend or do something fun and uplifting instead of engaging your brain because it’s gone into that exhaustion mode. It’s looking to heal and repair and rest and renew all the neurotransmitters.

How the Gupta programme uses limbic retraining in order to heal chronic fatigue syndrome 

Ari Whitten: Beautiful. So let’s talk about practical solutions. I know you have mapped out this whole paradigm for us, and out of this paradigm of what are the causes and the underlying problems, physiological and neurological problems, you’ve developed a solution out of this paradigm. I know that you’ve actually done research on it and published research and that the results are extremely impressive. Can you talk about your method? Limbic, and amygdala, and insular retraining and what kind of tools it uses, why and how it works.

Ashok Gupta: We have the Gupta program. The Gupta program essentially has three components: the three R’s, as we call them. Retraining the brain, relaxing the nervous system, and reengaging with joy.

As a starting point, this first cycle of the brain we retrain it using some pretty novel techniques. It’s different to CBT, so it’s not CBT, but it’s actually training the brain and the body to actually come out of that vicious cycle. So that’s the first part of the retraining.

Then the second part is relaxing the nervous system, so we use deep relaxation techniques and meditation in order to kind of calm the whole system. Re-engaging with joy is directing the mind’s attention away from how the body’s feeling and keeping that vicious cycle going, and enabling the brain to actually take a rest from a vicious cycle.

We’ve had a few medical studies done on this, although we’re looking to do a large study. We did our own clinical audit, which found that 2/3 of patients who continue with the treatment reached 80-100% recovery. We also did a small study with the Mayo Clinic, although there was a slight flaw in that study in the sense that they didn’t use our trained therapists to deliver the treatment, but it still showed a good result. Then we did a study in Spain which should be published in early February, which showed that, once again, 2/3 of patients who used the treatment went on to make a very good recovery, an 80-100% recovery.

We’re looking to raise $200,000 to do a large scale trial because we do believe that we’ll be able to show a really good result with these conditions. We’ve had a few studies just about to take off and then not quite happen, so we’re still actively looking for partners to do this with. We’re very excited to do it.

Ari Whitten: Awesome. If anybody’s listening, and you have the funds, and you’re interested in funding something like this, I want to make the point that this is a really great place to fund research. I think this has amazing potential to help a ton of people. So if you’re interested in funding something like this, reach out to Ashok. Where can people reach out to you, by the way?

Ashok Gupta: They can go to our website, which is and there you can find free videos and more information about everything that we’re doing. You can sign up to the free videos, find out lots of information, and there’s also lots of information about our research. Our medical papers are there and how we explain the condition. So that’s how they can reach out and find out more. We’re just about to start a three-month coaching program, so it’s a home study course, which people can get treated at home, and then we have a three-month webinar series where they tune in every week live with myself, and we go through all the different tools and techniques. Until we get a large scale trial we are offering a money back guarantee on it as well. If you use it for a year, no benefit, fine, return it, and you can use that money on another treatment.

Ari Whitten: Okay. Are they two separate things, or it’s the same thing?

Ashok Gupta: It’s one package. You get the three-month coaching and the home study course together in a package.

Ari Whitten: Okay, and that is the Gupta Program with the three R’s: basically how to retrain your brain and get yourself out of chronic fatigue syndrome.

Ashok Gupta: Yes, absolutely. As part of that we have an active forum, we have practitioners that can work one on one with people, so it’s a whole package of different things.

Ari Whitten: Beautiful. So, it’s very brain focused. The three R’s: tell me again what they are?

Ashok Gupta: It’s retraining the brain, relaxing the nervous system, and reengaging with joy. It is a holistic program because in the relaxing the nervous system we talk about anti-inflammatory diet, we talk about pacing, we talk about sleep, daylight, being in nature, so all of those things come under the banner of relaxing the nervous system. Diet’s an important part of that.

Ari Whitten: Beautiful. Awesome, I love it. So, where can people go? Just direct to the website?

Ashok Gupta: Yes. They can just go there and they’ll find all the information, sign up to the videos, and see everything else that we do.

Ari Whitten: Wonderful. Well, thank you, Ashok. It’s really been an enormous pleasure to have you on the show and to have this discussion with you, and I really appreciate you sharing your wisdom with my audience.

Ashok Gupta: Yeah, great. I’m honored you invited me, and it’s been a lot of fun. So thank you. Thank you, Ari.

Ari Whitten: Wonderful. Enjoy your night.

Ashok Gupta: Great, take care.

Ari Whitten: Bye.

Ashok Gupta: Bye.

How Your Brain And Nervous System Control Fatigue – Show Notes

What ME, CFS, and related syndroms are, and how they are related. (6:14)
What lead Ashok to conclude the brain is the primary cause of fatigue (10:10)
What the main causes of CFS are (16:41)
Why Ashok has identified the brain to be the crux of fatigue (23:08)
How the brain has a role in classic symptoms of chronic fatigue (26:00)
Why fatigue is a protective symptom (29:34)
How adrenal fatigue figures into what Ashok is teaching (33:58)
The spectrum of fatigue and where adrenal fatigue fits in (42:12)
How hypothyroidism can be a symptom of chronic fatigue (49:02)
How the brain is in hibernation mode in CFS patients (51:07)
How the Gupta Program uses limbic retraining in order to heal chronic fatigue syndrome (53:25)


If you want to know more about the Gupta programme, check it out here

Treating Fatigue by detoxing your environment │brain fatigue│How Your Brain And Nervous System Control Fatigue,
One way to make sure you remove the triggers is to cleaning up in your environment. Listen to the podcast with Dr Evan Hirsch how to detox your environment.
Cover image │brain fatigue│ Mitocondria And Fatigue: The Real Cause Of Fatigue,
If you want to know more about what other parts of your body control your energy levels, check out the Mitochondria and Fatigue: The real cause of fatigue podcast with Dr. Sarah Myhill

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