Today I want to discuss serum endotoxin levels in relation to type 2 diabetes. I don’t believe there is any hope of understanding the cause of this disease without reference to gastrointestinal health and translocation of endotoxins to the liver. It is the liver, after all, that is on the front lines when your intestines “spring a leak,” and it’s here that dysregulation of glucose and cholesterol occurs.
I want to reference a Finnish paper that was published in the journal Diabetes Care in 2011. (1) Like a number of papers since, the association between serum endotoxin and diseases we categorize as part of metabolic syndrome was found to be a very strong one.
These researchers followed 7,169 people between 25 and 74 years of age for a little over ten years beginning in 1997. These folks were recruited from five geographical regions across Finland.
At inception, all participants underwent a variety of tests to measure cholesterol (HDL, triglycerides, LDL), gamma-glutamyltransferase (GGT, a measure of liver and bile function), fasting glucose, C-reactive protein, blood pressure and levels of serum endotoxin. Also measured were BMI, waist circumference and waist-to-hip ratio.
Of the 7,169 individuals tracked, 537 were confirmed diabetics when the study began. Over the ten-year follow-up, 462 of the remaining 6,632 people were newly diagnosed with type 2 diabetes.
At the start of the study, these scientists noted that serum endotoxin levels were higher in the diabetics in contrast to those free of the disorder. Over the course of ten years, those who went on to develop diabetes also had consistently higher endotoxin levels than those that didn’t.
These researchers also noted that serum endotoxin load significantly correlated with elevated C-reactive protein plasma levels, decreased HDL and increases in triglycerides. Non-diabetics had a mean HDL level of 54 and fasting triglycerides of 118. In contrast, those that went on to develop diabetes had mean HDL levels of 47 and fasting triglycerides of 178.
As you know from my series on heart disease, I don’t buy into the hypothesis that cholesterol directly causes heart disease. Disordered cholesterol, like improper glucose control, is a symptom of liver dysfunction, itself a result of endotoxin load and not its cause.
BMI, waist circumference, waist-to-hip ratio and blood pressure were also higher in the group that went on to develop diabetes. However, this isn’t always the case as there are plenty of normal-weight people who go on to develop this disorder.
After statistical adjustment, these researchers noted:
“In this large prospective cohort we show that endotoxemia is associated with increased risk for clinically incident diabetes. Importantly, the risk was independent of established diabetes risk factors, i.e., glucose, lipid, and CRP levels, as well as BMI. It was also independent of factors known to affect serum endotoxin activity, i.e., cholesterol, triglyceride, and HDL cholesterol concentrations, as well as smoking. Interestingly, despite the linear relation between endotoxemia and the number of parameters defining the metabolic syndrome, high serum endotoxin activity was still associated with an increased diabetes risk.”
Now, most of you reading this won’t be surprised by this as I covered the link between endotoxemia and diabetes here. I obviously agree with these scientists that any theory that seeks to explain why diabetes develops has to take translocating gut microbes into consideration.
Where I part company with these, and many other researchers, is their emphasis on explaining these raised endotoxin levels by focusing mainly on chylomicron formation. Yes, eating fat, or to be more precise, longer-chain fatty acids, increases chylomicron formation. I explained that process in part three of my heart disease series.
However, as I also explained, that’s how long-chain fats are absorbed. It’s as normal to form chylomicrons or lipid rafts after eating fat as it is for your pancreas to produce insulin in response to carbohydrate ingestion or for your fat cells to release fatty acids to fuel energy needs between meals.
There will always be some level of endotoxin that slips through when chylomicrons are formed. That said, this becomes a much bigger concern in the presence of bacterial overgrowth anywhere in the small intestine due to gut dysbiosis.
Nonetheless, in the presence of an intact gut wall due to a healthy beneficial gut flora population, those chylomicron remnants with their load of inactivated lipopolysaccharides (LPSs) are safely excreted in bile and feces via the normal workings of a healthy liver.
Of course, the operative phrase here is “intact gut wall.” An unhealthy gut barrier always results in an unhealthy liver. Once this occurs, the liver becomes incapable of performing many of its hepatic functions, including proper glucose or cholesterol control.
So again I must emphasize that there is another major route that gut pathogens use to reach circulation: the paracellular route between gut epithelial cells. This route, not chylomicron formation per se, is the pathological state when it comes to endotoxin translocation.
Increased intestinal permeability is not normal or healthy. Chronic translocation of gut pathogens, day after day, year after year, taxes the detox functions of the liver.
Any hypothesis about diabetes that does not reference increased intestinal permeability and the liver is incomplete. Endotoxemia is not about the normal formation of chylomicrons in the absence of gut dysbiosis. Otherwise, all fat, from “evil” saturated fat to supposedly “heart healthy” polyunsaturated fat to monounsaturated fat, must be implicated as a cause of types 2 diabetes as they all contain long-chain fatty acids and form chylomicrons when absorbed.
Now to be fair, these researchers didn’t only implicate fat:
“High intake of fat or carbohydrates does not promote only endotoxemia, but also production of LPS transporting proteins and receptors. This “metabolic endotoxemia” has been shown to initiate or promote obesity, insulin resistance, metabolic syndrome, and finally diabetes. Whatever the sources, the current study clearly indicates for the first time an association between endotoxemia and incident diabetes.”
I can assure you that the only reason these researchers mentioned carbohydrates is because they’re Finnish. If they had been American, I doubt mention of carbs would have made it into the final draft. Instead, you would have been subjected to statements about the “well-known” effect of saturated fat to cause disease, make delinquents of your children, grow horns on your spouse’s head and cause politicians to lie (like they’d need any excuse).
It would have been helpful had these researchers specified which carbohydrates they were referring to, although I suspect they mean refined sugar. While I certainly don’t recommend going hog-wild on refined sugars, I consider that less of a threat to gut and liver health than gluten consumption, but I won’t belabor the point here.
The cholesterol markers noted in the Finnish diabetics are common findings in those suffering from metabolic derangement. Low HDL and high triglycerides are not unusual to see in these populations. A conundrum for those putting the blame solely on saturated fat is that many of these markers, not to mention glucose control, improve on low-carbohydrate or Paleo-type diets which, as a rule, have greater levels of saturated fat intake than recommended by many health “experts”. (2) (3)
The question, at least in relation to fatty acids, gut dysbiosis and endotoxemia is which fats are protective of the liver? Conversely, which fats are likely to accelerate damage to cells in this organ once intestinal gut-wall integrity is breached?
Chronic endotoxemia equals chronic inflammation equals lots and lots of free radicals. In a liver subjected to oxidative stress, it is sheer dietary lunacy to recommend substituting saturated fat with polyunsaturated fatty acids (PUFAs). These fats, when incorporated into cellular lipid structures, including those in the liver, are most prone to lipid peroxidation when subjected to free radicals.
It wasn’t surprising to me that during the Rose Corn Oil trial, two people in the corn-oil group developed diabetes. (4) As polyunsaturates increase intestinal permeability and damage cells when exposed to oxidants, how could it have been otherwise? (5)
Failure of the public and health “authorities” to know or acknowledge this has been an unmitigated health disaster, although very profitable for certain economic interests. Apart from high omega-6 intake, I shudder to think how many people out there are popping omega-3 fish oil capsules like candy because they’ve heard how good they are for health.
Yes, Americans are eating way too many omega-6 fats in relation to omega-3s. However, you don’t correct this lopsided ratio by increasing your omega-3 intake. You fix it by reducing your omega-6 consumption. That requires cutting out processed foods (all of them loaded to the gills with these fats), avoiding fried foods in restaurants and fast-food joints and substituting saturated and monounsaturated fats for PUFAs when cooking at home.
Yes, omega-3s are anti-inflammatory, but that’s because they suppress immune function. If your body is trying to fight a gut infection, what sense does it make to suppress the very system responsible for fighting it?
Ray Peat wrote an informative article a while back titled The Great Fish Oil Experiment that you can find here. I recommend you read it to keep your gut, liver and brain from suffering the consequences.
Chris Masterjohn also wrote on the subject of essential fatty acid intake, but it requires a payment of $15 to access. You can, however, find the article abstract here.
When it comes to gut health and your liver, PUFA intake should be kept to a minimum. I strongly recommend you leave the fish oil and/or flaxseed oil supplements on the store shelf.
As for cod liver oil, Chris Masterjohn has this to say:
“Until high-quality human data are obtained examining the effect of cod liver oil on lipid peroxidation and taking into account its vitamin content, it makes sense to use cod liver oil instead of fish oil, but to use it only in the small amounts necessary to obtain needed fat-soluble vitamins or to obtain a modest amount of DHA during pregnancy.”
Translation: if you are not pregnant or are not vitamin A and D deficient, there is little reason to take it. If you do, be sure to minimize your intake of other PUFAs and include saturated/monounsaturated fats in your diet to protect your liver.
While antioxidants like vitamin E and C, and glutathione precursors like N-acetyl cysteine, help mitigate oxidative damage, you would still do well to limit PUFA intake as much as possible. Even the best antioxidants will have a hard time neutralizing free radical damage when oxidative stress is high.
This advice is especially important for those of you dealing with gut issues. Your gut walls and livers are already under enough oxidative stress dealing with gut dysbiosis; adding PUFAs to the mix just makes things that much worse and will increase your odds of developing diabetes.