Hoping to fix your broken metabolism? Bad news…you can’t

Are you trying to fix your “broken metabolism”?

Is your appetite out of whack?  Maybe you’ve put on quite a few pounds or you have a difficult time losing weight.  Blood glucose running a little high?  Maybe you feel like you don’t have enough energy to get through the day or you need to rely on coffee to do so.

Luckily for you that you recently read on the internet that you have a “broken metabolism”.  The symptoms define you to a T.  No wonder you’re always hungry…your cells aren’t getting the energy they need.

And alas, there’s a way to fix it.  All you need to do is fix your leaky gut.  Since your gut is leaky, bacteria are getting in to your bloodstream and gumming up the works.  By firing up the immune system and causing chronic inflammation, your leaky gut is making you insulin resistant.  No wonder you’re always hungry and have dysregulated blood glucose levels.

Well, I hate to be the bearer of bad news, but that’s not correct at all.  Taking glutamine, probiotics, and fiber while restricting carbohydrates isn’t going to seal up your leaky gut and fix your metabolism because it’s not broken.  Not even a little bit.

A broken metabolism isn’t even a thing

If you’re a frequent reader of my blog you know that I’ve written often on leaky gut and metabolic dysregulation.  If not, check it out here and here.  So then what’s the scoop?  How can I write about a broken metabolism when it’s not even a thing?  That’s easy, I don’t.

Your metabolism isn’t broken, it’s doing exactly what hundreds of thousands of years of evolution have shaped it to do.  It’s just that those years shaped it for conditions it’s no longer operating in.  Not getting what I’m laying down?  A couple of examples…

Imagine you buy a brand new Hyundai Accent and try to tow a 30 foot boat with it.  Not gonna happen.  But is your Accent broken?  No, you’re trying to use it for something it wasn’t designed for.

If your TV remote isn’t working because you put the batteries in backwards, is it broken?  No, it’s working precisely in the way it was designed to work.  You’re just using it wrong.

These examples illustrate the problem.  Your metabolism isn’t broken, it’s just been removed from the operating conditions it’s ideal for.  Your metabolism is doing exactly what it was designed to do, you’re just using it wrong.

Taken from: http://www.paleoplan.com/wp-content/uploads/2015/02/Evolution-of-stress.jpg

Modernization screwed us

Before we jump in to metabolism, it’s important to begin with a cursory explanation of evolution.  Biological processes are driven by the way environmental factors trigger the expression of genes in organisms.  This, in turn, causes an organism to respond and adapt to it’s environment.  In some instances the adaptation leads to successful reproduction and the passing on of genes, other times it doesn’t.

Over time, organisms of the same species with genes that convey an advantage to them over others are more likely to reproduce and those genes get passed on to future generations.  For others with genes that convey no advantage, they’re less likely to reproduce and those genes may eventually disappear.  This is how a population evolves, and over time it can cause substantial changes to the way an organism looks and functions.

Over a very long amount of time, advantage genes tend to show up more and more in a population while disadvantage genes become less and less prevalent.  This is great if the environment stays exactly the same, but it can cause problems when the environmental factors that selected for advantage genes experience drastic changes.  Enter now.

Metabolism from an evolutionary perspective

If we take a look back at the environment of our recent evolutionary history, we can see a pretty clear picture as to why our metabolism isn’t broken.  Even as little as a thousand years ago, food in our environment was scarce and required substantial energy to find.

Humans with a voracious appetite that ate every time they came upon food were far more likely to survive famine than humans that weren’t that driven to eat.  Other factors also directly shaped our metabolism.

A thriftiness with carbohydrate, at the time the hardest to find macronutrient but one that quickly fuels our brain and immune system, also provided an advantage to gene holders.  The induction of insulin resistance when carbohydrate intake was low assured the holder of those genes that their brain and immune system would be given preference to the glucose in the blood.

There’s no doubt that these factors conveyed significant advantages to our ancestors.  Those were the days of scarce food and death by infection.  As such, they’re fairly prevalent today, a mere blink of an eye away from those ancestors in evolutionary terms.

So let’s break down what our past environment shaped us to be.  A chronically hungry, carb seeking, insulin resistant, quickly becomes inflamed, and stores fat easily hominid who thrives under high levels of physical activity.  Doesn’t sound broken to me.

Taken from: http://ecx.images-amazon.com/images/I/81WEQNTEEVL.gif

Your metabolic owner’s manual

When you buy a new car there’s always an owner’s manual in the glove box.  Open the owner’s manual up and you’ll find a warning: Don’t tow a boat with your new Hyundai Accent.  So it would be very useful to have an owner’s manual for your metabolism so you can use it properly.

I won’t jump in to a complete user’s guide to the human body in this blog, but it’s in my plans down the road.  I’ll just cover this “broken metabolism” myth and show you why it’s not broken.  Spoiler alert, the gut’s involved.

The gut is a disgusting wasteland of bacteria.  Some bacteria contain a molecule in their cell wall called lipopolysaccharide, or endotoxin.  When endotoxin enters our circulation, the immune system goes on high alert.  This induces an inflammatory state and causes high blood glucose, insulin, and triglycerides.  Did I mention there’s a ton of endotoxin in your gut?

This state of elevated inflammation, blood glucose, insulin and triglycerides is called metabolic endotoxemia.  It’s basically the insulin resistant state and many many moons ago it was a very advantageous state…under the right environmental conditions…when you couldn’t get your blood glucose up in to the 300s.

Taken from: http://www.schneiderclinic.com/img/leaky-gut-syndrome.jpg

Getting endotoxin from the gut in to you

There are a couple of ways you can get enough endotoxin in to your body to cause metabolic endotoxemia.  But first, you have to be overweight, obese, or type 2 diabetic for it to be clinically relevant.  Endotoxin enters the circulation of healthy individuals, but it’s efficiently processed by the gut and liver and doesn’t lead to long-term metabolic disturbance.

The traditional way that you’ve likely come across, and something everybody and their mother thinks they have, is through a “leaky gut”.  If you have an infection in your gut, SIBO, circadian disruption, or consume excess alcohol your gut will “leak”.  This increases endotoxin in the blood and promotes metabolic endotoxemia, conserving glucose for the brain and immune system.

Acutely, high calorie and high fat meals cause an increase in endotoxin in the blood, even in healthy men(1, 2).  Chronic exposure to either of these 2 conditions typically leads to weight gain and obesity in people genetically susceptible to packing on the pounds, likely due to changes in the microbiome associated with these dietary patterns(3).

The dietary pattern changes the microbiome which, in turn, alters intestinal permeability.  It also increases the amount of bacteria with endotoxin in your colon.  The better to make you insulin resistant with, my dear.

But a leaky gut isn’t the only way to experience endotoxemia from these 2 dietary conditions.  High fat intake increases endotoxemia whether you have a leaky gut or not.

Taken from: https://openi.nlm.nih.gov/imgs/512/285/3270440/PMC3270440_JOBES2012-879151.003.png

Fat intake and endotoxemia

The ketogenic diet is often used as a therapy for those experiencing obesity and Type 2 diabetes because the lower carbohydrate content prevents wild fluctuations in blood glucose.  While the tighter blood glucose control is definitely an advantage, try to go off of it for a day and see what happens to your blood glucose.

People like to differentiate between the ketogenic diet and the high fat diet used to induce insulin resistance in mice.  That diet is more like a processed Western diet which leads keto-dieters to poo-poo the idea that a ketogenic diet will lead to poor glucose handling.

Sorry to burst your bubble, keto-dieters, but one of the mechanisms through which LPS enters the circulation is by hopping a ride on chylomicrons(4), which transport dietary triglycerides in to the lymphatic system from the gut.  This is the other way of getting endotoxin in to the body and doesn’t require a leaky gut.  Higher fat intake means greater chylomicron production and greater endotoxin absorption right along with it.

And if you’re wondering, yes, this does increase inflammation.  Whether you’re ketogenic or just eating a Western diet, more chylomicrons means more endotoxin sneaks in through the gates.  However, it’s important to put this in to context.

While inflammation increases during a high fat diet whether it’s ketogenic or not, the ketogenic diet lacks carbohydrate.  In the context of a ketogenic diet, blood glucose and inflammation levels are kept in check since dietary carbohydrate is being restricted(5).

But, ingest carbohdyrates and you’ll see both markers increase.  Endotoxemia, per se, doesn’t cause pathological levels of inflammation unless blood glucose levels climb.  Interrupt your ketogenic diet with a nice helping of carbohydrate and that’s exactly what happens.

This isn’t great if you want to interrupt your ketogenic diet with a large carbohydrate dose from time to time.  But once upon a time it provided a big advantage when the seasons changed and dietary carbohydrate availability took a seasonal nosedive.  Conserving that carbohydrate for the brain and immune system while storing any excess away for later use is highly advantageous.  Not so much when carbohydrates are ubiquitous.

Image result for ketogenic circadian

Taken from: http://atvb.ahajournals.org/content/atvbaha/29/10/1571/F4.large.jpg

Ketogenic diet and circadian disruption

Another drawback of a ketogenic diet is that it induces circadian disruption(6, 7), likely because it simulates starvation.  This may not be a big issue for someone exposed to a normal day/night light cycle, but it can make things worse for someone with improper light exposure.  Several “symptoms” of a ketogenic diet tell this story.  Specifically, increased alertness, less sleep and lower body temperature.

The first 2 were distinct advantages to our ancestors because they would promote the search for food when it became scarce.  Whether you are starving or ketogenic, the brain needs glucose and promoting alertness and reducing sleep are 2 ways to increase your search for it.  Decreasing heat production also promotes survival by increasing energy efficiency.  That way, more energy can go towards the search for food.

This isn’t to say that one can’t eat a ketogenic diet, just that the long term implications aren’t fully understood.  I’d even say a short-term ketogenic diet may be more appropriate from an evolutionary perspective.  Good in the short-term doesn’t mean good in the long-term.

There’s probably a wide range of variability between individuals in their tolerance to a long-term ketogenic diet.  People in areas where the ketogenic diet was simply the way of life, like the Inuit, are probably better adapted to it than your average American.

It’s important to understand that there are probably some genetic differences that make them better adapted to that type of diet long-term.  One of these involves a resistance to the ills of circadian disruption due to large seasonal variability of the day/night cycle in their environment(8).  People whose ancestors thrived under these conditions are more likely to have genetic advantages that were passed down to their offspring.  That doesn’t mean they apply to you.

Taken from: http://www.frontiersin.org/files/Articles/92314/fmicb-05-00190-HTML/image_m/fmicb-05-00190-g002.jpg

Is metabolic endotoxemia affecting you?

As you can see, your metabolism isn’t really broken from a leaky gut, it’s doing exactly what evolution shaped it to do.  And your gut doesn’t even need to be leaky for this to happen, excess dietary fat and calories will also do the trick.

You have to keep in mind that not everyone is going to be affected equally by metabolic endotoxemia.  It certainly makes sense that most people would be prone to it given the numerous advantages it conveyed in the past, but that doesn’t mean everyone is.  I’m sure a few stragglers snuck through, and over the course of the last 50 years they’ve been seeing the advantages.

This probably brings you to the question of whether or not metabolic endotoxemia is affecting you.  I think there are a couple of ways to figure this out.  First, if you’re overweight, obese, or a Type 2 diabetic…that’s a pretty good indication.

Second, there seems to be a strong association between fasting triglycerides and endotoxin levels.  I think high fasting triglyceride levels are a good indicator of metabolic endotoxemia.  While there is no specific data, you want definitely want fasting triglycerides under 100mg/dL, 75mg/dL is better.  Anything above 150mg/dL is indicative that there’s a problem.  I know the reference range for fasting triglycerides is <150mg/dL, but I don’t believe that to be an ideal range.

Finally, an oral glucose tolerance test can be very useful in determining how well your body processes glucose.  For the test, you measure your fasted blood glucose and consume a beverage containing 75g of glucose.  You also measure your blood glucose at 1 hour and 2 hours after ingestion of the drink.

Your blood glucose should drop back to the fasting level within 2 hours.  If it doesn’t, or if it skyrockets above 180mg/dL after an hour, this may be indicative of metabolic endotoxemia.  Of course, discuss this with your healthcare professional before undertaking or basing your therapeutic approach on it.

Reversing metabolic endotoxemia

If you’re experiencing metabolic endotoxemia, reversing it should be an immediate goal as poor glucose control long-term is associated with a diverse array of poor health outcomes.  There are a number of things you can do on the lifestyle end of things to help.

  • Eat fewer meals.  Eating 3 meals instead of 5 has been shown to decrease endotoxin levels in both lean and obese subjects(9).
  • Decrease total calories and fat intake(1, 2)
  • Decrease fructose consumption(10)
  • Decrease alcohol consumption(11)

In addition, setting your circadian rhythms and syncing your master and peripheral clocks is critically important.  Circadian rhythms regulate the strength of the inflammatory response to endotoxin while endotoxin-induced inflammation strongly influences circadian rhythms(12).

Other factors regulated by circadian rhythms, specifically cortisol and melatonin, are important to keep inflammation and the damage associated with it to a minimum.  Truth be told, this could have a blog all to itself, which is why I’ll be covering the circadian influence on SIBO soon.  Clearly, removing an active infection or overgrowth is critical to remedying metabolic endotoxemia.

It’s interesting to me that there are a number of things we do today that open us up for progressively greater levels of metabolic endotoxemia as we age.  Most people eat a high fat diet, eat far too often, and do many things that open them up to circadian disruption.  This includes improper light exposure and poor meal timing.

We’re also much more resilient to circadian disruption when we are younger and seem to lose our inherit rhythm as we age.  The consequences of these patterns seem to be pretty clear and may help explain the increased risk of chronic inflammatory diseases that comes with age.


Despite what you’ve read on the internet or at a seminar, metabolic endotoxemia and insulin resistance aren’t the consequences of a broken metabolism.  In fact, they’re the direct consequences of evolution shaping our metabolism to work better in the environment that our recent ancestors lived.

Granted, nowadays this “mode” of our metabolism can cause some pretty devastating consequences to our health, but that doesn’t mean your metabolism is broken.  This may seem like a minor distinction to you, but it’s a valuable distinction to drive better behaviors.

Even in healthy people, endotoxin makes its way from the gut in to the bloodstream.  There doesn’t appear to be significant consequences to this in healthy people: problems tend to arise only when people are overweight, obese, or Type 2 diabetic.  If you remove these 3 conditions, endotoxin still translocates from the gut to the blood but your metabolism and glucose handling improves.  So is it really the problem?

Saying your metabolism is broken is kind of a cop out.  It implies that there’s nothing you can do, or worse, that all you have to do is fix one minor problem and everything will run smoothly.  There’s quite a bit you can do, and one has to wonder if many of the symptoms that people experience are made worse because of the choices they make after they realize there’s a problem.

Think about this…It’s extremely common for people who believe they have SIBO or IBS to restrict carbohydrates and increase fat intake.  This will reduce the mucus layer separating bacteria from the intestinal barrier and promote the growth of bacteria that contain endotoxin in your colon.  Spreading meals out over 5 meals a day will further increase endotoxin levels in the blood.

Circadian disruption is also a major factor as high fat diets, including ketogenic diets, can phase shift circadian clocks.  Every protective mechanism in the gut, from acid and enzyme secretion to tight junction proteins and antimicrobial peptides, are controlled by the circadian clock.  Setting an appropriate schedule of feeding/fasting, light exposure, exercise, and layering all 3 together in the proper way can improve symptoms bigly.


3 thoughts on “Hoping to fix your broken metabolism? Bad news…you can’t

  1. Emma says:

    Hi, I just started reading your work. It’s very interesting and thank you for your efforts. My comment on this article is the seeming curve-ball of recommending decreasing fructose consumption due to a study in kids with NAFLD…
    Are you familiar with the study data showing that orange juice taken with a high-fat, high-carbohydrate meal prevents “meal-induced oxidative and inflammatory stress, including the increase in endotoxin and TLR expression.” https://www.ncbi.nlm.nih.gov/pubmed/20200256
    It would seem blanket recommendations to reduce fructose, certainly on that one study on already unwell children, may not be ideal.

  2. cincodm says:

    Yes, I’ve read the OJ article. But there are multiple studies and it’s universally held that high fructose consumption induces endoxotemia.

    Primate animal model https://www.ncbi.nlm.nih.gov/pubmed/23783298
    Mouse model http://www.fasebj.org/content/31/1_Supplement/894.3.short
    A discussion of mechanism which is the same between us an animal models http://onlinelibrary.wiley.com/doi/10.1002/hep.23212/pdf
    A paper on how fructose changes the microbiome, which is the mechanism by which it increases endotoxemia http://www.fasebj.org/content/31/1_Supplement/894.3.short

    And of course, the OJ study http://ajcn.nutrition.org/content/91/4/940.full

    While the study in people with OJ is interesting, it doesn’t negate the studies on fructose for 2 reasons. First, OJ isn’t particularly high in fructose, only 27% of the sugar in OJ is fructose. Although 300 cals of OJ may be pretty close. Second, that study showed a reduction in endotoxemia after a single high calorie meal with OJ. A change in microbial composition takes far longer than that and that’s how high fructose consumption alters endotoxemia. Also, the people in the study were healthy and normal weight. In an overweight or obese person, who likely already has the microbial composition that makes fructose consumption lead to greater endotoxemia, these results don’t apply. So, that study shows that taking 300 cals of OJ reduces endotoxemia in a healthy person after one meal. It says nothing about what it does to people prone to endotoxemia or after repeated OJ intake over time.

    Thanks for reading and thanks for your comment.

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