Interview with Marek Doyle

On Adrenal Fatigue, Metabolic Mapping, Rate-Limiting Factors, Heart Rate Variability, and much more.

I came across Marek Doyle when he posted this helpful comment in response to my Niacin article.

Great to see an article discussing all of the 'forgotten' benefits of Niacin. The only real question appears to be: why don't more practitioners make use of it? This is where I commonly see hesitation for two reasons.

The first on the basis that "yeah it clearly has a whole load of benefits, but might it cause insulin resistance in some people?" This is due to some scientific articles finding the opposite effect - as in, an increase in insulin resistance - which leads them to hesitate in making use of it. But, if we can break with Evidence-Based Medicine's futile hunt for The One True Effect and instead consider the mechanism here, we can easily reconcile this apparent dichotomy....

Niacin inhibits the release of fatty acids from adipocytes (fat cells), which means that there is less free fatty acids in the bloodstream. If this is timed to occur ALONGSIDE meals, where glucose from the meal is being absorbed into the bloodstream, this avoids the unwanted competition for uptake at cellular level (cells can only take up a certain amount of energy at any one time... if they don't have any fatty acids to handle, they remain sensitive to insulin and take up more glucose). A major knock-on effect is that we avoid the energy excess in the bloodstream (which would normally see the liver having to handle this excess, and turn the excess glucose into fat, aka De Novo Lipogenesis). Result: increased insulin sensitivity at the liver/muscles/organs and less fat deposition in the liver.

Taking in then (and not at night) gives the fat cells a chance to empty themselves overnight (in fact, they release more fatty acids due to the 'niacin rebound'); this is a time when fatty acid release from the fat cells is helpful to maintain energy supply and also means that, the next day, these fat cells start the day emptier (which means they can better 'sponge' up any excess energy following meals... this, of course, is the key in protecting against energy excess, described above). Naturally, using Niacin at the opposite times can have the opposite effects... A great discussion of the benefit of timing Niacin is in this free article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234709/.

The other cause of hesitation is the unpleasant flushing effects. This is due to high levels of an inflammatory chemical called Prostaglandin D2 (PGD2). This is where identifying any inflammatory triggers can be helpful, but can also be directly managed with agents that inhibit prostaglandins in general, such as Aspirin or Gotu Kola, although most effectively with agents that directly work against PGD2, such as Luteolin (I've written in more depth on this here.

Hope that's useful for those who are interested in the benefits but had concerns about the seemingly-conflicting data!

Marek writes on a variety of interesting and important health subjects, so I invited him to this interview and I’m grateful that he accepted.

We cover a lot of ground, and I’m sure there is something here for everyone.

With thanks to Marek Doyle.

Health & Humanity | Marek Doyle | Substack

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1. Marek, could you please tell us about your early years and what sparked your interest in nutritional therapy and human physiology?

It was the one type of science that I always found both fascinating and useful. As a child, I played a lot of football and swam competitively and was always curious in the basic patterns I’d see, such as feeling sluggish if I ate to close to an event or having a better nap after a game on Sundays if I ate a high-sugar snack. I can’t say I followed through with any of these observations when I was younger, although I definitely applied a lot of principles when competing in Muay Thai; turns out being leaner and stronger is huge help when trying to beat an opponent with more natural talent!

But my interest was always more than just wondering if I could improve performance. A real deep dive into nutrition and human physiology means internalizing how the metabolism works, but also scrutinizing basic science and evolution then reconciling the principles that play out here with the wisdom bestowed upon us from traditional healing approaches.

2. Can you walk us through your journey from personal trainer to becoming an expert in personalized nutrition?

I started working full-time in this field in 2005 and, at that time, my main focus was working with athletes. I was qualified as both a personal trainer and nutritional therapist, although naturally these titles blurred into one another as I spent my time putting together training protocols and dietary plans.

Although I really enjoyed the measurable feedback that we get in the athletic area – whereas you might perceive that dietary changes have improved your mood and you might feel like you have better energy, taking 0.2 seconds of your 100m time is measurable and undeniable – it turned out that life had other plans for me.

The first area that I really started getting good results in was fat loss. Naturally, that’s something of a crowd-pleaser and so word-of-mouth meant that, before long, it was mainly members of the public that I was working with. And guess what? Some got great results, but a lot did not. It clearly wasn’t that the protocol I was using was ‘ineffective’, but something was stopping some individuals from responding the way that others did.

Cue the start of the investigation. An era marked by plenty of hope, hype and lots of dead ends. But also some gold. With each and every piece of the puzzle that I managed to fit into place – and the turnaround in the individual I was working with – I would typically get a half-dozen referrals from contacts that individual had made previously in their journey. And, surprise surprise, some of them would respond really well and some of them would not. Cue more and more rounds of discovery, further turnarounds in challenging cases, run this cycle on repeat and then add in a couple of my own challenges and, before I knew it, I’ve spent a decade now dealing mainly with the ‘complex/chronic’ cases.

3. You've mentioned experiencing your own health challenges. How did these experiences influence your approach to nutrition and wellness?

They say that ‘most research is me-search’ and I’m guilty as charged here. But I guess you could summarize the effect of these issues in that the first challenge showed me what was missing from the mainstream approach – “your blood tests say you’re in great shape” – while the second showed me what was missing from my own.

I suffered with what is lazily called ‘adrenal fatigue’ in 2007 from living a stressful life, holding a lot of internal stress, sleeping too little and training too hard ahead of a Muay Thai bout. In 2012, I got two hits on my spine in the same week while living in a mouldy flat and it left my nervous system in a quite a state, with some wild insomnia.

With this second challenge, I made the naïve mistake of assuming that the attending to the insults that prompted my decline would be sufficient to see me back to full function. Logical, sure, but it turns out that there was more going on. There’s always more going on. One principle that I had to learn the hard way is that, while it’s important to consider what pushed me ‘over the edge of the cliff’ into dysregulation, the real value is exploring what factors dragged me to the edge of that cliff in the first instance.

For me (like many others), I had so much buried stress in my system. But, as long as my system compensated for this – ie. my adrenals ran on overtime and so did my top-down-regulation (this is where the prefrontal cortex continually quietens down the amygdala) – I felt fine. The inflammatory response to mould is well known to reduce blood flow to the brain. The spinal injuries, and the physical tension they induced, compromised this further. Enough to push me over the edge. Suddenly, the regulatory apparatus couldn’t put in the extra shifts that were needed, the stress signals were no longer contained and all this stress signaling hijacked my system into over-activation. And thus, a disproportionate response (hideous insomnia and delimited deployment of the stress response, with the downstream costs that come with this).

Of course, while these were key players in my case, it doesn’t need to be mould or a physical injury that triggers these types of issues. When we are ‘on the edge of the cliff’, then any insult can be enough to temporarily disable our compensatory responses. Off the cliff we fall. This could be a cold, a run of some sleepless nights or a phase of unusually high stress.

Acknowledging this pattern obvious makes us aware of just how many people in modern society lives on the edge of this cliff. But it also helps provide an explanation for anyone who is struggling to understand why getting a cold last autumn could mean that they can no longer tolerate various burdens that were previously of no consequence. The key thing to remember here is that these burdens always had a cost, but that our systems have exquisite systems in place to compensate. Until the compensatory systems are pushed into failure and the genie is let out of the bottle.

4. Your research seems to focus on building a comprehensive model of personalized nutrition. What drove you to pursue this particular area?

Mainly observing the reality of what I saw, time and time again. That I could see give the same recommendation to two individuals with identical symptoms yet, time and time again, one would respond and one would not. In other words, that the mainstream approach – to use the ‘best’ protocol – was failing a huge number of people who needed support.

I always felt a strong desire to determine why this was, and how we could know ahead of time who would benefit (and thus, what recommendations to make to who). This is the basis for personalized nutrition.

And this is where my research pulled me away from the ‘one pill for every ill’ model, which focuses on the ‘best’ or ‘most effective’ drug for a specific labelled condition (with the label awarded on the basis of symptoms). There was no focus on identifying what was driving these symptoms, and how to identify which step of which pathway was causing such issues.

Fortunately, we’ve got all these systems of medicine that have worked for thousands of years. All of them focus on the person in question and match the treatment to their needs. All take into account what steps may be needed for the person to enter a healing state, none looked to the pill to do the healing. In short, all of them personalized their approach. They often used metaphors and language that we judge as falling short of the modern scientific ideal, but there was always a clear focus on understanding the basic needs of each individual and on using the patterns established over centuries to guide them to effective remedy.

This is where personalized medicine thrives or fails on our ability to understand why each intervention actually works and also on our ability to build a suitable map of the individual’s metabolism (specifically where any burdens or blockages exist). The details can get pretty heavy, but the principle is really simple; build a sufficient map to reliably determine what each individual needs at that point in time.

5. You've developed what you call a "methodical and objective process of map-building." Can you explain what this means and how it benefits your clients?

One of those things that can be difficult to explain but it’s something that makes intuitive sense (so basically the reverse of modern medicine!). To be more specific, this refers to the process of assessing an individual’s needs so that we can provide what is needed and avoid.

I would always start by taking a case history. Here, we are getting background on the key patterns that need our attention and forming an idea of what questions we need to answer in this case. A great example here is when people have reacted in an unexpected way to treatment or failed to respond to something that they clearly ‘should’ have responded to; this tells us where we need to know more – where the map is incomplete – and allows us to furnish this ‘map’ with this individual’s signature responses to inflammation, to stress. We can also uncover patterns unique to them, such as what responses we see in their gut and in their sleeping patterns when subject to physical stress, emotional stress, or even what responses we see when they no longer in ‘emergency mode’ (a lot of people actually struggle with this, but I digress). We can then add to this picture by considering the specific responses of their nervous system to different interventions (eg. those that improve energy availability).

Once we have a suitable idea of how their system responses to different environmental inputs, we can then conduct a screening of the patterns we are seeing on a day-to-day basis and compare this to what responses we’d expect to see.

We can then focus in on these ‘unexpected’ responses and add context to them. This is where functional lab results (notably, the Organic Acids Test) and the Heart Rate Variability (HRV) figures can be invaluable. They allow us to make conclusions on if a pathway is limited by dysfunction (or nutrient deficiency etc.) or if it actually functions but has been shut down in an attempt to adapt to high demands elsewhere. In other words, if we know what the system is trying to do with its resources, we can see which patterns are simply the body doing what its evolved to do in challenging circumstances and which patterns are a dysfunction of a specific pathway.

(An example here: if someone cannot lose weight, this may be because their body won’t lose weight – the individual has eaten too little for too long, the system senses a lack of energy resources, aka a high risk of starvation, and our system simply protects energy reserves in the way it has evolved to in these circumstances – or because their body can’t lose weight (because long-term stress, and the high adrenaline output that comes with it, has downregulated the adrenaline receptors in fat cells so that they can no longer respond to requests to mobilize energy).

The main benefit is that we can finish the initial consultation with a clear idea of why we are seeing the patterns and which of these issues will respond to ‘direct’ intervention and which are simply downstream consequences of the disinvestment that occurs when our systems do not have enough resources. Most importantly, we can determine what milestones we are working towards and provide the individual with personalized metrics to monitor their progress (and also alert them to any patterns we expect to encounter as they touch down at the next stage).

Another way of saying this is that they get to actually understand what’s happening and form a realistic idea of what their journey will look like, versus playing the game of ‘pick a guru and then spend the next few months of your life finding out if his ideas work for you’.

6. In your work, you often mention the importance of identifying "rate-limiting factors." Could you elaborate on this concept and why it's crucial in personalized nutrition?

In essence, identifying the rate-limiting factor is a more detailed (and more useful) substitute of the more common question we ask: what is stopping this particular individual from the wellbeing they desire?

As an example, I may have two individuals, Amy and Bryony, both of which are dealing with fatigue and brain fog and both happen to show a shortage of B1 upon testing. B1 is playing a contributing role in both of them. However, Amy has good sleep hygiene, digestion is mainly OK and her lifestyle is not overly stressful. B1 is the rate-limiting factor for her; provide a generous amount and we expect her to feel a major difference from that day onwards. Meanwhile, Bryony is working 16 hours a day, has her laptop open until midnight, then wakes at 5am for a 10k run. She has crippling intestinal pain and hasn’t passed a stool in days. In her case, B1 will help but isn’t actually the rate-limiting factor; she doesn’t have a fair chance to respond.

So this is about identifying not only what needs tending to, but which of these interventions is going to make a difference to how they feel, to the symptoms they are experiencing and to their wellbeing in general.

It also means that we can answer the second of the two golden questions that all individuals want to know the answer to. The first relates to what do they need to do. The second is when will they feel better; identifying what specifically is holding them back, at this point in time, allows us to provide a realistic answer to that.

We should also recognize that any health journey involves reassessing what the rate-limiting factor is at any point in this journey; by definition, you clear up the blockages at step one of a pathway and you get to see how steps 2-6 are working (and if any need unblocking). It also helps us recognize that there will always be multiple issues present – if any one major system goes offline, it takes the others with it – but there will be some key levers that will provide a platform for improvements and others that will directly initiate the improvement.

7. You've talked about the relationship between stress, cortisol, and inflammation. How does this interplay affect overall health, in your opinion?

The interplay has been central in every single individual with chronic issues that I’ve ever worked with. One very obvious truth – but one that is rarely discussed – is that stress automatically induces inflammation and inflammation automatically induces stress.

When the system detects stress – by which I mean whenever our alarm centres in our nervous system detect a need for more energy resources than they currently have – they will induce the stress response. This involves both the vagus nerve and activation of the hypothalamic-pituitary-adrenal (HPA) axis. A drop in vagal tone means that you’ve removed the brakes on the inflammatory response; all immune cells are now primed for inflammation. The first step in the activation of the HPA axis is the release of a chemical called CRH; this just so happens to activate inflammatory activity, especially in mast cells (they have receptors specifically for this hormone).

However, the most powerful way that stress drives inflammation is via endotoxemia. This happens in chronic stress. A stress response is all about getting more energy from circulation and one of the ways that it does this is by opening channels in the cells that line our gut. It does this in order to grab more sugars and salts from the gut, but the cost of doing so is that little fragments of dead bacteria - aka endotoxins - can now enter the circulation too.

Now, unless you have good cortisol activity, this is where we can expect a potent inflammatory response as these endotoxins interact with our immune cells. The irony here is that the endotoxins also downregulate cortisol receptors; let’s pin this topic as we’ll come back to it shortly.  

Meanwhile, inflammation causes stress through a number of mechanisms. First of all, activated immune cells are extremely energy thirsty. This is going to steal our energy, which automatically means we have less energy available relative to the perceived demand (the physiological definition of stress). On top of that, inflammatory cytokines can compromise energy production in the mitochondria. This means that no- immune cells are less able to tap into our energy supplies, thus permitting the immune cells to grab more than their usual share. So quite an elegant mechanism here, but one that can come with a major stress load on the system (this is, again, through reducing the amount of energy that's available).

One very important thing to focus on here is the role of cortisol. Cortisol is always released during stress response to a) help us cope with the stress, but also b) to counter the pro inflammatory effects of the stress response. As we touched on above, chronic stress can result in this chronic endotoxemia pattern. This is important because as soon as you've got this pattern, the cortisol receptors are down-regulated and now you can't actually regulate the inflammatory activity that occurs with each round of stress.

Not only that, you haven't got the cortisol to turn off the stress response, leading to a self-perpetuating cycle of inflammation, driving stress, and stress driving inflammation without the in-built tools designed to turn it off. This is why supporting cortisol is such a key thing for anybody with chronic conditions. And it's important to state that cortisol has a very important role here in helping our system.

It's so often demonized as ‘the stress hormone’, which is extremely unfair. Yes, whenever there is stress, there is cortisol, but cortisol is not driving the pathology here. Cortisol is actually being released to limit the pathology and much in the way that ambulances are on the scene of any accidents, but they're not causative. I’ve written previously about this confusion of cortisol (here) and why it is so important to support its action whenever there's chronic stress or inflammation… which, as we've touched on above, is pretty much the same thing.

8. Your approach seems to challenge some conventional wisdom about nutrition and health. What are some common misconceptions you often encounter in your field?

There's obviously a lot of misconceptions in this field. We can see that from the results that we tend to get, but there's three misconceptions that stand out. And they are related. The main one relates to this idea that the body is some sort of machine, wherein components fail and need fixing. This is something that we see especially in this weird era of specialism where individuals get passed from one specialist to the next, each looking at this tiny section of the body to see if the individual qualifies for a particular label. And when they don't, they pass them on to the next in line to see if the other area is ‘the problem’.

So much of our medical resources are spent on trying to name the problem. What if we stopped looking at in in this way and instead recognize that the body is self-healing, provided there's no obstacle stopping it from doing so. That's the role of a holistic practitioner to actually help recognize where these obstacles are (and what needs to be done to remove them) but then let the healing process occur.

Now, what's so damaging about this idea – that a component of the machine failing and we must hunt down the part that has broken - is that we end up going in wild goose chases trying to find The Root Cause. And this is an exercise in futility. There has never been a single occasion where a major problem has occurred in one system of the body and has not immediately affected adjacent systems.

(Examples: as we've already touched on, if your adrenal function is compromised in any way, then we can expect rampant inflammation to start playing out elsewhere. But, if there's any gut issues, then this can have a huge array of downstream impacts on the inflammatory process, on vagal nerve activity, and even on mitochondrial performance. If there is anything physically affecting the function of the liver, then we can anticipate problems in detoxification of the body, but also energy metabolism and the digestive process.)

So we're clearly seeing this interconnected system. And this is where, should we pose that same old question – what is THE root cause of all our issues? - the answers we get back are going to be disappointing.

Equally, we can easily then get caught up in search that runs parallel to this hunt for THE root cause; this is the elusive hunt for The Perfect Protocol. This assumes that, once we've identified a problem, all that is now required is a lavish dose of science and this will deliver us the protocol that will swiftly-and-efficiently remove such dysfunction and allow us to ride off into the sunset.

However, there's two issues with this that I think which I hope are very evident. One being that there is almost always going to be a number of legacies that any original dysregulation will have left elsewhere. These legacies will need ‘tidying up’ if we want to avoid the usual frustration in these circumstances (that there's tiny improvements but the dial doesn't really move overall). And, secondly, it also assumes that there is a linear pathway between having chronic issues and wellness. It treats this protocol as some sort of magic button that restores us from chronic disease to a state of wellness. The things is here that, when we actually observe how the human body heals, it will always do so in stages and we're typically looking for the appropriate support to allow their system to move to its next milestone and then update the support we provide accordingly.

9. You've mentioned the importance of Heart Rate Variability (HRV) in your practice. Can you explain why you believe HRV is such a valuable metric?

It is the best measure we have of the function of our autonomic nervous system, which determines how we use our energy. It’s fair to say that energy metabolism governs everything in the human body, but that the autonomic nervous system governs energy metabolism.

Quick primer on the autonomic nervous system. There are essentially two branches to the autonomic nervous system: sympathetic and parasympathetic (with this second branch driven by the vagal nerve). And there’s three main states that our autonomic nervous system will play out in the body: those that we can call rest and digest, fight and flight, or freeze.

The first state, rest and digest, is where we have parasympathetic dominance, which means our system is demobilised. It has the energy availability to meet the demand. t's not scrambling for energy because there's no need. It has what it needs. 

Fight and flight is a state of sympathetic dominance. This is where there is not enough energy to meet the demand. It is where the body is scrambling to find extra energy, and attempting to dump more energy into circulation so that we are better prepared to meet a challenge. One aspect of this response is a re-allocation of resources and a reduced investment in non-emergency tasks.

The third state, often deemed freeze, is one where the stress on the system is no longer just high, it's excessively high. There is too big a gap between the energy that’s available and the perceived demands.  It's too big for a human stress response to bridge the gap. So this is where the system once again demobilises and enters a state of shutdown. It's not the preferred response, but it’s the chosen response given the dire circumstances. A key aspect of this response is the near-total disinvestment in non-emergency tasks.

Heart Rate Variability (HRV) indexes whether our system is mobilized or demobilized (aka sympathetic or parasympathetic). Providing that we add context to the figures and not treat them as black-and-white – something all the HRV apps out there do - then this allows us really good objective measurement of where an individual is at and also allows us to track responses to interventions that the individual may otherwise miss.

Let’s look at how this can help us on the frontline.

One of the features of that freeze-type stress response is that a lot of the internal sensory transmission are placed on hold. We aren't necessarily thinking about our hunger. We're not feeling emotional in this state. We're largely going to be feeling fatigued and flat (as an aside, this causes a huge amount of problems for these individuals in navigating the medical system because they won't fit the caricatured box of what it looks like to be stressed, yet they'll exhibit major stress reactions to anything that starts to improve the situation and thus be given a label that ends in ‘disorder’ or ‘syndrome’). These are individuals for whom it can be very difficult for them to detect anything subtle because, on a neurobiological basis, they're not going to have a fair chance to do so. HRV measurements allow us to get a handle on what options are currently realistic given their system is investing their energy resources.

HRV measurements also let us know what potential challenges we might encounter as a result of generating improvements in energy security in the system, aka reducing stress. Specifically, when people are in a freeze-type response and they improve their energy security, the areas of the system that are initiating the shutdown no longer do so. They take their foot off the emergency brake, if you will. This now allows them to exhibit all the classic features of the classic stress response. This is an inevitable step for anybody that starts their journey in a freeze state but is so often misinterpreted as a bad reaction to something (a verdict given even though there may already be tests demonstrating that the individual was severely deficient in the nutrient we've just provided them with).

Equally, it's quite common to see people coming outside of a sympathetic response and dropping down into rest-and-digest for the first time in many years. It's not the rainbows-and-unicorns state that it's often painted to be. There's often going to be a whole load of circuitry in the brain that's now allowed to fire up, which is great (and ultimately what we want). But, during the transition, it can actually be quite uncomfortable. People can find themselves feeling much more emotional than usual, feeling aches and pains in the way that they weren't when the adrenaline was flowing.

In both cases, having HRV data before and during such changes allows us to know what we should be prepared for, what sort of signs we should look out for and allows me to explain these things ahead of time so that each individual need not be caught off guard.

10. In your research, you've found that individuals with low HRV often struggle to benefit from certain interventions. Why do you think this is the case?

So this is something that we see time and time again when individuals attempt to undertake any procedure that places stress on the body, such as anti-microbial programs, detox procedures and even fasting.

It's not to say that there isn't a place for a lot of these things; in the case of antimicrobial programs in particular, they will actually end up making the difference between somebody feeling decent and feeling great. But, if the system doesn't have the resources it requires to undertake that process, then there is very little chance that we're going to see the result that we're after.

What I mean here is that, if there is a particularly strong sympathetic state, the body is diverting its resources towards readiness and vigilance; it’s focused on surviving. It's not worried about investing this extremely valuable resource – energy - in any process that may be beneficial to its wellbeing in weeks to come because, according to the signals it's currently receiving, there may well not be a next week. Unless it resolves the emergency right here and now.

So we can see this play out in reduced investment into the gut. This means less movement. And that means that there's going to be a whole lot more opportunity for fermentation to occur. These are ideal conditions for the undesirable microbes, so we would be fighting them ‘on their home turf’, as it were. Equally, if there is insufficient permission granted to the immune system, then there is no fair chance for the immune cells to go ahead and score the victory that we're hoping for here. However, we still can get all of the unwanted symptoms that come with the process.

The key thing here is that HRV allows us to quantify with precision as to the autonomic state of the body. That is to say, how it's investing its energy so that we don't need to toss a coin when choosing interventions. We don't need to cross our fingers and hope that this protocol will be the thing that pulls people from the depths of despair (and then be disappointed when it doesn't). We can now know ahead of time and we can focus our attention on the areas that are needed, which is to support the energy security (aka to reduce the stress of the body so that it is now in a healing state).

That would be the main message here. Don't expect the body to conduct any healing unless it's in a healing state. HRV helps us know whether it's in a healing state or not.

11. You've written about the potential drawbacks of the "evidence-based medicine" paradigm. What are these drawbacks and what alternatives do you propose for a more personalized approach?

Firstly, I recognize that most people are surprised to hear me criticize Evidence-Based Medicine (EBM) due to the misconception implied by its very title… the implication that it’s medicine, based on evidence. And we all want the medicine we receive to be based on evidence, right?

However, EBM is a very specific paradigm that aims to eliminate superstitious thinking and human bias, which it does through its Hierarchy of Evidence. This places Randomized Controlled Trials and Meta-Studies at the top, and expert opinion at the very bottom.

It’s fair to say that the EBM approach is a reasonable tool for helping formulate public health policy, but the drawbacks are the obvious ones: if you purposefully exclude expert opinion from your knowledgebase, your knowledgebase will lack expertise. I understand the reason for wanting to limit the potential for bias, but this is impossible; it’s still humans designing the studies, deciding on what the inclusion/exclusion criteria will be and passing a decree on which adjustments to apply to the raw data. So we need to consider that, given that we cannot exclude the potential for human bias from the process, do we want such influence to be in the hands of those who have spent decades refining expertise and building understanding of the nuances of their subject? Or in the hands of under-slept, over-caffeinated graduates who have zero frontline experience and are conducting nutrition research even though they can’t even feed themselves a healthy diet?

Beyond this huge flaw, there are also some assumptions that compromise the conclusions produced. The main one being that there is One True Effect to any given intervention, and that we can find out what this figure is if we run enough trials and average out all the recorded responses.

So an alternative approach I would suggest is one that:

• exploits both existing expertise and existing evidence, and recognizes that evidence can take many forms

• caters to the fact that people with the same condition can respond differently to the same intervention

This means integrating mechanistic reasoning; working out why some people are responding and why are others not. This comes back to true principles of science; making observations, producing hypotheses that might explain them and then subjecting them to falsification (‘if this hypothesis is true, what else would be true?’). This is an approach that is based on what works and why, and then makes decisions on the best course of action for any given individual. Ironically, this basically describes every single form of medicine that has lasted the course (and has done a great job, unlike the EBM experiment of the last 30 years, which has resulted in an unprecedented decline in human health).

12. In your article about probiotics, you challenge the notion that there's "no proof probiotics work." What's your perspective on the effectiveness of probiotics?

This ties into the way that EBM dogmatically treats a singular figure produced by meta-studies as the best form of evidence, rather than asking what the evidence is actually telling us.

My article on this is here, but it essentially outlines the ridiculous premises in the meta-study in question, in that it lumped a load of patients with different types of IBS. We already know that some forms of IBS benefit from probiotic supplementation, and others are made worse. Guess what happens when you take the outcomes from both types of study and average them out? You end up with an average that sits close to zero effect and you conclude that ‘probiotics don’t work’.

But that is not at all what the evidence actually tells us. It tells us that different types of GI issues responded in very different ways to probiotic supplementation. In other words, it supports what we have seen on the frontline since forever: that probiotics are a powerful intervention that can produce striking results, but we’ll only see this when the microbiome is the rate-limiting factor (ie. when a) the bacterial population of the gut is holding back progress and b) there is a fair chance of responding to the protocol). You can’t expect to take a whole load of studies, using different types of probiotics in different types of GI conditions, and then average out all the responses here to ‘discover’ that One True Effect.

Probiotics are invaluable. One way of thinking about the bacteria in our gut, which total 1.5kg by weight, is to consider it an organ system in its own right; based on its influence to so many other areas of the body and to health in general, this is a fair concept. The key thing here is that it is an organ system that we have tools to modify and upgrade, and probiotics are that tool.

13. For those interested in following your work or potentially working with you, what's the best way to stay updated or get in touch?

I am putting together articles here on Substack and my page is marekdoyle.substack.com. I’m also on Instagram with the handle @marekdoylenutrition. I’ve also got plenty of articles on my website, www.marekdoyle.com/articles.

For those who want to know more about working with me, they can drop me an email (marek@marekdoyle.com) and I will send them my New Starter Guide, which outlines how I do things, what they can expect and basically help them decide if this is the right course of action for them.

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Baseline Human Health

Watch and share this profound 21-minute video to understand and appreciate what health looks like without vaccination.