How chronic high fat food consumption causes gut problems

With the renewed interest in the keto diet, many people regularly consume high fat food. But just because something gives you short term benefit doesn’t mean that there are no long term consequences. Overall, if a person loses weight on keto and can’t do so on a regular diet, it’s probably great for them.

Unfortunately, I don’t think people stick to the keto diet over the long term. Maybe they do it for a few months and diverge. Or maybe they do it on the weekdays and come off on the weekends. Either way, if you go keto you should stay keto.

A new study just published on high fat diets show that 5 days of a high fat diet increases absorption of LPS. LPS is a component of the cell wall of bacteria in our gut. So, this means that LPS is sneaking across the gut barrier. But I wouldn’t refer to this as leaky gut, as you’ll soon see.

High fat food increases endotoxin

In the study, participants consumed a weight maintenance control diet for 2 weeks. Consequently, they were fed a high fat meal and put on a high fat diet for 5 days that also maintained weight. Again, after 5 days, they consumed the high fat meal again. Macro ratios for the diet and meal were:

  • Control diet was 55% carb, 30% fat, 15% protein
  • High fat meal was 820 cals (25% carb, 63% fat, 12% protein)
  • High fat diet was 30% carb, 55% fat, 15% protein

Researchers measured serum LPS prior to the high fat meal and 4 hours after during both high fat meal challenges. A 4 sugar intestinal permeability test was also performed. Since all participants followed the same protocol, each acted as their own control group.

Despite no change in intestinal permeability as measured by the 4 sugar test, serum endoxotin doubled. This is a bit troubling since all participants were healthy (BMI=23) and free of dyslipideia or other metabolic disease. In other words, overweight or obese people likely see greater problems.

But how does LPS get in to the blood without leaky gut? I discuss the 2 primary types of intestinal permeability in my free course 3 Common Causes of Leaky Gut. Check that out to get up to speed.

High fat foods leaky gut

Not a leaky gut from high fat food

What most people think of as leaky gut is paracellular permeability. In it, the tight junctions that hold the cells in the gut together fail. The 4 sugar test will measure this, and people classically think of this as leaky gut. But since the 4 sugars didn’t cross the barrier, the gut wasn’t “leaky”.

However, there is another way to increase paracellular permeability. Passive absorption of a substance occurs when the concentration on one side of the barrier is higher than the other side. Things aren’t “leaking” in this form of permeability, they are let across.

So based on this study, 5 days of high fat feeding increases the amount of LPS in the gut. The concentration increases to the point that LPS passes from the gut to the blood.

What this means for keto dieters

So what does this mean for people doing the keto diet? I don’t think it means that going keto is bad, per se. However, increasing the amount of LPS in your gut and serum isn’t a gut thing. The biggest problem is when you decide to go off the diet.

Multiple lines of evidence point to increased fat intake altering the microbiota to favor an increase in gramnegative bacteria. This is the type of bacteria enriched with LPS. This jibes with the research above.

In the context of the keto diet, I don’t think this is a big issue. The problem comes when you do something else that increased permeability, particularly in the colon. Alcohol definitely does this, so people going keto probably want to abstain from alcohol.

But an even bigger issue is that hyperglycemia coupled with low insulin promotes paracellular permeability in the colon. This is the worst case scenario as most of your microbiome resides in the colon. Therefore, so does most of the LPS.

This assuredly happens to people when they abruptly come off keto. Don’t believe me, it’s simple enough to test. And people have reported it as “physiological insulin resistance”, a normal adaptation to a keto diet. But your colon doesn’t care about that, it only sees hyperglycemia and insulin resistance.

Boom, leaky gut in the worst of places. It’s interesting to point out that the results of the above study indicate the colon wasn’t involved. So this would likely lead to a far worse effect than a doubling of fasting endotoxin.


Based on the anecdotal evidence scattered about the internet, there is no doubt many see health benefits from a keto diet. Be that as it may, our gut responds in a consistent way to a chronic diet of high fat food consumption: increased LPS in the gut.

This doesn’t mean that you shouldn’t follow a keto diet. But it does indicate that if you are eating a keto diet, you should stay keto. Don’t diverge on the weekends and definitely reconsider alcohol intake.

Over time, if you plan to transition to a more balanced diet, take your time. Introduce carbs slowly, and measure your blood glucose. Many report they fell worse on carbs after following a keto diet long term. But this may have more to do with how rapidly they introduce carbs rather than an inherent intolerance to carbs.

6 thoughts on “How chronic high fat food consumption causes gut problems

  1. Primal says:

    The high fat diet studied was not low carb, none of the diets in the study were. In a 2000 calorie diet that 30% represents 148 grams of carbohydrate. There was no keto diet in the study, not even low carb.

    • cincodm says:

      No one said there was. If you check out the review cited, increasing fat intake increases LPS in the gut. In fact, high meat in general will do that but that is typically from the bacteroidetes phylum which contains many beneficial microbes. The phylum is gram negative which contain LPS.

      If you have some mechanism by which a keto diet would alter this effect, I would love to hear it. From the perspective of a keto diet, having more LPS in the gut isn’t bad, per se. It become bad when one decides to bail on the diet and go on a carb binge. Under insulin resistant conditions, hyperglycemia causes leaky gut and that LPS will enter the bloodstream.

      Even in this diet, the increase in LPS wasn’t necessarily pathological, but it did change the way muscle metabolized fat and glucose.

      This isn’t an indictment of keto, it’s evidence that if you are keto you should stay keto. If you decide to come off, a slow transition is best. In the absence of clinical trials showing an effect, it’s important for people considering an approach to also consider potential drawbacks. But you don’t need a clinical trial to measure your blood glucose, and if you are currently keto, an OGTT will confirm the blood glucose response which is certainly not a great situation.

      If you read the blog, that is the perspective I’ve written it from. It’s not anti-keto, I’ve done keto before and have may friends who do. It’s so that people considering the diet that also may follow the approach of “screw it” on the weekends that this is a bad idea.

      • Primal says:

        As happens often, extrapolations are made from data that aren’t necessarily supported.

        Ideally we’ll just look at a study where CHO is truly low. It’s been shown pretty conclusively that the combination of fat and carbs in a hypercaloric diet leads to inflammation and disease. This study looked at people eating these diets.

      • Primal says:

        In this five day study, yes, not hypercaloric. The reason that any diet works is because people cut calories. You can eat just about anything and as long as you stay under your energy needs, you’re not likely to have any serious chronic health issues. Most chronic diseases are storage problems… What does the body do with the extra calories at the end of the day? No extra calories, no issues… For the most part, obviously there are exceptions.

        Can you share any data from the gut of a person on a VLC or ketogenic diet long-term? Again, the data that we’re looking at here is from a mix of high fat along with a relatively high CHO intake.

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