Bottled Inflammation


In this post, I discussed how unlikely it is that normal digestion of long-chain fatty acids is the source of the pathogens initiating arterial plaque formation. If anything, I showed how protective chylomicrons are in preventing just that. This then leaves us with increased intestinal permeability as the most likely source of translocating pathogens.

While today’s post will focus on the role of dietary fat in “leaky gut”, I once again need to emphasize that once you have intestinal dysbiosis, any food you eat may increase the translocation of bacteria, yeast, larger food molecules, etc. into the liver and to a smaller extent, systemic circulation. The more often you eat, the more frequently this happens.

Since small-gut dysbiosis increases hunger and cravings by its negative effects on gut hormone secretion and nutrient absorption, reigning in overeating can be challenging until dysbiosis is tamed via dietary change and resolution of bacterial and yeast overgrowth.

Increased intestinal permeability will allow long-chain fatty acids, that would normally only be incorporated into chylomicrons, access to the blood flowing to the liver also carrying with them antigens and bacteria that will provoke an immune response. As more fat is now reaching the liver, more cholesterol will be synthesized to export it. As I said, changes in cholesterol levels are a marker of endotoxemia, not the cause of it. I’ll have more to say about this in an upcoming post.

OK, let’s look more closely at the anatomy of the small intestinal gut wall:


Courtesy: Advanced Nutrition and Human Metabolism, fifth edition.


Here you see the finger-like projections or villi that make up the absorptive layer. In the bottom-left-hand corner, you see a close-up of the one-cell thick layer separating the contents of the small intestine from the blood vessels leading to the liver, and the lymphatic vessels that chylomicrons enter to transport long-chain lipids to systemic circulation.

Notice the straight line separating each cell or enterocyte. These are tight junctions that under normal conditions prevent pathogens and larger molecules from slipping through. Here’s close up view of these junctions:


Courtesy: Exercise regulation of intestinal tight junction proteins


Absorption of nutrients should always occur through the enterocyte or said another way by transcellular transport. That is how long-chain fatty acids are absorbed and where they are incorporated into chylomicrons. Likewise, short- and medium-chain fatty acids should travel across this route as well as amino acids and simple sugars. Paracellular transport should be limited to water, electrolytes and some trace nutrients.


Courtesy Widipedia


The names of the various protein complexes responsible for maintaining these tight junctions are highlighted in the blue box above. These tight junctions (TJs) exist throughout the intestinal tract, including the colon. One of the many roles of beneficial gut flora is to maintain the integrity of these TJs and the proteins responsible for their proper functioning. One way they do so is by preventing the gut wall from being colonized by pathogens that break apart these protein structures either physically as in the case of yeast overgrowth, or by increasing oxidative stress and inflammation.

Occludin and claudin-1, claudin-2 and claudin-3 are mainly responsible for maintaining gut barrier function. Of these two protein classes, claudins are the most important. Mice who are bred to lack claudin die within one day of birth. (1)

We know that gluten opens these junctions. (2) Plant lectins are also disruptive. (3) Alcohol, especially binge drinking, also compromises intestinal integrity. (4) Small intestinal dysbiosis, and the inflammation that results from such an overgrowth, directly impacts these protein structures for the worse.

All oxidation from gut inflammation has the potential to affect these proteins. Oxidation is a normal process of cells that use oxygen to produce energy from various substrates, including those cells lining the intestinal tract. This process is called oxidative phosphorylation, and it would take an entire book to cover. Should you be interested, this Wikipedia entry is a good place to start. As this article makes clear, the gram-negative pathogen E. coli is quite adept at thriving in an oxidative environment.

Most oxidation within cells will be harmlessly converted to water but not all. Two very harmful intermediate substances produced are superoxide anion and peroxide known collectively as reactive oxygen species or ROS. These are highly unstable agents. They have the potential to damage DNA, proteins, fats and intestinal cells, including those producing protective mucus. There are a number of built-in defenses that cells use to guard themselves against these harmful substances, but suffice it to say that these defenses can be overwhelmed in times of intense free radical production as in an immune response.

Anything that increases oxidation in the intestinal tract will also disrupt beneficial bacterial populations. Especially vulnerable are Lactobacillus species that predominate in the small intestine. These bacteria do not handle oxidation well, certainly not as well as gram-negative pathogens like E. coli. Bifidobacteria species in the colon are also negatively affected.

One substance that can be extremely oxidizing is fructose. Fructose forms half of the sugar molecule and can comprise anywhere from 42% to 90% of high-fructose corn syrup depending on the formulation. We are well adapted to handling moderate amounts of it in its natural form where it comes packaged with fiber, antioxidants, vitamins and phytochemicals. Strip it of these protective substances during refining and we become far more prone to its ill effects. In large quantities, fructose produces lots of free radicals in those intestinal cells that are able to metabolize it because of its ability to rapidly degrade ATP to uric acid. (5)

Fructose, gluten, lectins and alcohol are not the only dietary components that increase oxidative stress in intestinal cells. Some fats do too.

You’ve all heard of saturated, monounsaturated, and polyunsaturated fats. The difference between these fats comes down to whether the carbon atoms that compose them contain double bonds.

Saturated: These fats do not have any double bonds between carbon atoms, and are saturated with hydrogen atoms. Saturated fats are very stable and not prone to oxidation when subjected to heat or free radicals in the body. For this reason, they are ideal for high-temperature cooking. Because they are straight in form, saturated-fatty-acid chains pack together readily and are solid or semisolid at room temperature. Saturated fats are found in animal fats and in tropical oils like palm and coconut oil.

Monounsaturated: These fats have one double bond which means two carbon atoms in the chain are double-bonded to each other. For this reason, they lack two hydrogen atoms. At the double-bond, these fats form a kink, so they don’t pack as easily as saturated fats. They are therefore liquid at room temperature although will congeal somewhat when refrigerated. While stable, these oils are more prone to oxidation than saturated fats. Oleic acid is a common form of monounsaturated fat found in our food and is the main component of olive oil. Almond, pecan, cashews, peanuts and avocados are also rich in oleic acid as is lard. Lard is 44% oleic acid, 42% saturated fat and 10% polyunsaturated fat. As fats are typically classified by the predominant fatty acid contained in them, lard should be classified as a monounsaturated fat, not a saturated one.

Polyunsaturated: These types of fats have two or more double bonds and therefore lack four or more hydrogen atoms. Like monounsaturated fats, these double bonds are kinked so they don’t pack together well making them liquid even when refrigerated. Polyunsaturates can be further classified by the position of their first double bond in relation to their omega end. Polyunsaturated fats are called omega-6 fatty acids when their first double bond is in the sixth position from this position. Vegetable oils are very high in omega 6s.

Polyunsaturates with their first double bond from the third position of the omega end are called omega-3 fatty acids. Fish and flaxseed oils are both omega-3 oils yet differentiated by the length of carbon atoms they contain and their unsaturation.

These types of oils are extremely delicate and prone to oxidation when subjected to heat, light, pressure and free radicals in the body. They should never be used for cooking. Unfortunately, that is exactly what many vegetable oils are used for. They are routinely utilized in fast-food chains, restaurants and are common in processed foods.

All fats are combinations of different fatty acids. Canola oil, for example, is 62% monounsaturated fat, 6% saturated fat and 32% polyunsaturated fat. Butter fat is 56% saturated fat, 29% monounsaturated fat and 32% polyunsaturated fat.

Trans fats, implicated in both heart disease and cancer, are manufactured fats. They are made from polyunsaturated vegetable oils after the partial addition of hydrogen atoms to empty spots on their carbon chain. Olive oil and lard can also be subjected to partial hydrogenation to extend shelf life. Any lard you see that is not refrigerated is partially hydrogenated. Because hydrogenation straightens out the carbon chain, they have similar physical, although by no means biological, characteristics to natural animal fats. These are true Frankenfoods and should be avoided at all costs.

Your cells will reflect the type of fat you eat. Lipid peroxidation is the degradation of fats by oxidants leading to their damage and is not something you want happening to fats that are incorporated into your cellular structures. Of the fats mentioned, saturated fats are the least susceptible to this process.

Polyunsaturated oils, however, both omega 6 and omega 3, are particularly prone to lipid peroxidation by virtue of their missing hydrogen atoms. Omega 6 fatty acids are also inherently inflammatory.

While extremely delicate, omega 3 oils reduce inflammatory responses and are good for you as long as inflammatory stress in the liver is not an issue. However, omega 3s subjected to oxidation can be very damaging.

How do we know this? Because the fastest way to cause alcohol-induced liver injury in an animal model is to feed them fish oil along with their Hooch. If you are prone to binge drinking, I do not recommend that you wash down your fish or fish-oil capsules with alcohol.

Oxidation and Fatty Acid Composition

“Although diets that contain SFA [saturated fatty acids] and possibly MUFA [monounsaturated fatty acids] may protect the liver against toxic agents, it is unlikely that any public agency would recommend an increase in intake of animal fats.”

This quote is from a paper entitled: Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatoxicity by altering fatty acid composition of liver microsomal membrane in rats. Catchy title, no?

I chuckled and shook my head when I read this. Heaven forbid authorities tell the public the truth about the protective role saturated fats play in a liver subjected to inflammatory stress. Well, I’m not a member of the “health authorities” club so I’ll tell you that in a liver inflamed by endotoxemia, the last thing you need in your diet are fats that add to the problem and nothing adds to that damage like polyunsaturated omega 6 vegetable oils.

Now please don’t take this as a recommendation to stop eating polyunsaturated-rich fish. On the contrary, fish and the omega 3s they contain can go a long way in calming the inflammation raging in your intestines and liver as long as omega 6 fats are kept to a minimum.

I’m somewhat ambivalent about recommending fish-oil capsules, however. Knowing what I know about how nutritional supplements are warehoused and shipped in this country, you are gambling that these delicate oils have been handled properly before you buy and consume them. Companies like Amazon, for example, do not have temperature-controlled warehouses. If you take fish-oil capsules because you don’t eat fish, try to find a fish oil that you can buy directly from the manufacturer or was properly handled. The same holds true for flaxseed oil.

The protective role of saturated fat in alcohol-induced inflammation of the liver has been a dirty little secret rarely mentioned lest the public question the whole “saturated fats are bad” dogma. In a paper entitled Beef Fat Prevents Alcoholic LIver Disease in the Rat the following graph is displayed:



Here you see the results of a six-month rat bender on liver function. The corn-oil group had the worst liver outcomes, followed by the lard group (remember, lard is a predominantly monounsaturated fat). The least affected were the beef tallow group. These results have been replicated numerous times. (6) (7) (8) (9) (10) I could cite more studies but you get the picture.

In the presence of endotoxemia and liver inflammation, saturated fats are protective while polyunsaturates, especially omega 6 oils, are not.

To bring home this point I want to review an article that was published in May of this year. (11) To my knowledge, this is the first paper that links the intake of omega-6 vegetable oils in animals to increased intestinal permeability, but I could be wrong so don’t quote me on this.

As in earlier studies of this type, it found that rodents fed ridiculous quantities of alcohol were mostly protected from ill effects when fed saturated fat, in this particular case beef fat and medium-chain saturated fat. Medium-chain fatty acids are largely found in tropical oils made from coconut and palm. They have antibacterial and anti-fungal properties making them ideal for those battling small intestinal bacterial and yeast overgrowth.

Here is a chart detailing the composition of both diets. For diet composition data directly from the manufacturer, see this:


Courtesy: The Type of Dietary Fat Modulates Intestinal Tight Junction Integrity, Gut Permeability, and Hepatic Toll-Like Receptor Expression in a Mouse Model of Alcoholic Liver Disease


Here are the results:


White bars represent results before the start of alcohol feeding (first two weeks), black bars represent results after alcohol feeding (eight weeks). Note that ALT, a test that detects liver damage, is pretty much the same between the saturated fat (SF) and saturated fat with alcohol or ethanol group (SF+EtoH). The polyunsaturated corn-oil group had slightly better results without alcohol, but this changed dramatically with its addition. Fat accumulation was also worse in the corn-oil group as were levels of nonesterified free fatty acids (NEFA).

Like I said, this isn’t particularly revelatory. What caught my attention, however, is what happened to these mice in the two weeks before they were fed alcohol.

By the way, in this study, both the control and alcohol diet had the advantage of not containing fructose. I say advantage because when I read a rodent study that implicates saturated fat for all evil, including the rape of your sainted mother, inevitably sucrose, i.e. sugar, is part of the formulation and sucrose is half fructose.

Fructose causes oxidative stress in the intestines and liver. This is why fructose feeding is so effective at inducing obesity and metabolic syndrome in lab rodents. The fat invariably used in these high-fat rodent diets is lard, which is typically described as a saturated fat in these papers. This is not correct as you already know. While monounsaturated fat is more stable than polyunsaturated fat in the presence of fructose or oxidation, it is more prone to lipid peroxidation than saturated fat. What many of these studies show is that coupling excess monounsaturated fat with fructose is not healthy, but neither is overeating in general.

Returning to our study, the mice fed the corn-oil mixture ate much more during the first week than the saturated-fat group. This discrepancy narrowed somewhat by the second week. Nevertheless, the corn-oil group still had higher energy intake during the second week which leads me to believe that they were hungrier and already suffering from negative changes in the gut.

Once the alcohol part of the trial began, energy intake declined in both groups. I suspect this was due to increases in the cytokine tumor necrosis factor-alpha which induces wasting syndrome or cachexia. In the following fluorescence microscopic scans, you can see the different accumulations of liver fat in both groups represented by the whitish dots:

The saturated fat group both before and after alcohol consumption showed less fat accumulation in the liver than the polyunsaturated corn-oil group or USF group. What strikes me is how rapidly fat accumulated in the unsaturated fatty acid group in the two weeks prior to alcohol feeding compared to the saturated fat-fed mice.

As I explained here and here, fatty liver and the inflammation that results from it is a direct result of translocating gut pathogens. This requires increased intestinal permeability which is a direct result of disrupted intestinal tight junctions. With that in mind, feast your eyes on these charts:

All of these charts track the level of various tight junction proteins. Higher is most definitely better. In all cases, the saturated fat group had higher levels of these proteins in their ileum than the corn-oil group even before the introduction of alcohol. The ileum is that part of the small intestine nearest to the colon and the first to be colonized by migrating colonic gram-negative bacteria in cases of impaired intestinal movement.

As a side note, short-chain saturated fatty acids like butyric acid found in dairy products and butyrate, produced by beneficial bifidobacteria, are used by intestinal cells as “food”, nourishing these cells and maintaining intestinal gut wall integrity. Whenever anyone tells me that saturated fats are bad for my health, I enjoy asking them why is it that my beneficial gut flora produce them? I always enjoy the look of absolute befuddlement that crosses their faces, but then again, I’m easily amused.

The researchers of our mouse study theorized that the down-regulation noted in the corn-oil group was mediated by the pro-inflammatory effects of omega-6 fatty acids. Omega 6 has known oxidative effects on vascular cells and will activate inflammation in liver Kupffer cells. (12) (13) It is therefore not a stretch to believe they do the same to cells lining the digestive tract.

Apart from their negative effect on tight junction proteins, the pro-inflammatory effects of these fats will also negatively impact mucus secreting intestinal cells and beneficial bacterial populations.

In fact, polyunsaturated omega 6 fatty acids are the main fatty acids found in arterial plaque. They comprise over 50% of the fatty acids found here, with monounsaturated fat making up 30% and only twenty percent composed by supposedly “artery clogging” saturated fat. (14) The more omega 6 found in arterial plaque, the more likely it is to rupture and lead to either a heart attack or stroke. (15)

To sum up, does fat have anything to do with endotoxemia and heart disease? Yes it does. Any fat in the presence of gut wall dysfunction, along with protein and carbohydrate, will cause translocation of gut pathogens. The majority of these pathogens will end up in the liver creating oxidative damage and disease. A small portion will bypass the liver entirely and directly enter the bloodstream. In more advanced cases of “leaky gut” and subsequent hepatic damage, these pathogens will also escape the liver and enter systemic circulation. Cholesterol will try to neutralize these substances and repair the damage they cause in arteries, but along with other responding immune cells, form atheromas and fibrous caps. If unstable, these complexes can rupture producing a heart attack or stroke.

In populations where gut dysbiosis and endotoxemia are rampant, encouraging people to substitute highly reactive and inflammatory omega 6 polyunsaturated fats for saturated fat is nothing short of dietary madness and a denial of the basics of fatty acid structure and biochemistry.

The cause of heart disease is metabolic endotoxemia. Binge drinking, excess consumption of sugar, trans fats, overeating, omega 6 oils, tooth decay, respiratory infections, gluten, stress, aging, poor anti-oxidant status, cigarette smoking, etc. are all risk factors for cardiovascular disease because they can all negatively impact gut wall integrity and beneficial bacterial populations. Correcting dysbiosis through changes in diet and resolving bacterial and yeast infections while replenishing and maintaining beneficial gut flora populations is the only hope you have for preventing this potentially deadly disease.

In the next and concluding post, I discuss what role cholesterol has in this process.



Enig, M. G. (2000). Know Your Fats : The Complete Primer for Understanding the Nutrition of Fats, Oils and Cholesterol. Silver Spring: Bethesda Press.

Gropper, S. R., Smith J. L., Groff J. L. (2009). Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Cengage Learning.


Comments are closed.

Post Navigation