F-HFD: fructose enriched high-fat coconut oil diet
F-SO-HFD: fructose enriched high-fat soybean oil diet
HFD: high-fat coconut oil diet
PUFAs: polyunsaturated fatty acids
SO-HFD: high-fat soybean oil diet
Viv: low-fat, high-fiber rodent diet
“Look! It’s moving. It’s sa — it’s… it’s alive. It’s alive… It’s alive, it’s moving, it’s alive! It’s alive, it’s alive, it’s alive! It’s ALIVE!”
From the 1931 movie Frankenstein
Hello everyone! Yes I’m still alive and kicking and today’s post proves it! Hard to believe it’s been seven months since I last blogged, but there you go. How often I’ll be doing so from this point onward remains up in the air so don’t be shocked if I slip back into extended hibernation.
I’m sure you’re curious as to why I’ve decided to write again. Was there some incredible breakthrough in gut flora research that got my blogging juices flowing?
No, not really. Most published research over the past half year has pretty much confirmed findings that I’ve already written about.
This typing frenzy was indirectly inspired by an open access article that appeared in the latest edition of the British Medical Journal concerning the non-existent association of saturated fat with coronary artery disease:
“Saturated fats are not associated with all cause mortality, CVD [coronary vascular disease], CHD [coronary heart disease], ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats.” (1)
In other words, there is still no credible link between saturated fat consumption and heart disease or stroke risk contrary to what we’ve been consistently told for the last 50 odd years. There is, however, a very clear and statistically significant association between heart disease and intake of omega 6 vegetable oils that have been artificially saturated, i.e. trans fats. This isn’t really shocking as trans fats have been under increasing scrutiny for their harmful effects on human health.
But this meta-analysis wasn’t my main motivation for today’s post. Instead, it was the following press quote from the lead author of this study, professor Russell de Souza. He’s a registered dietitian and assistant professor in the Department of Clinical Epidemiology and Biostatistics with the Michael G. DeGroote School of Medicine at McMaster University:
“If we tell people to eat less saturated or trans fats, we need to offer a better choice. Unfortunately, in our review we were not able to find as much evidence as we would have liked for a best replacement choice, but ours and other studies suggest replacing foods high in these fats, such as high-fat or processed meats and donuts, with vegetable oils, nuts, and whole grains.” (2)
Yet these “other studies” being epidemiological in design, are just as useless for dispensing scientifically accurate nutritional advice as those now debunked observational studies that unnecessarily warned two—yes two—generations of people against eating saturated fat!
Now let me reiterate for the record that I’m not a proponent of high-fat diets, especially of the ketogenic variety unless medically necessary. I’ve made my reasons for this well known in other posts so I won’t belabor the point here.
Nevertheless, if the good professor’s own meta-analysis failed to find an association between saturated fat intake and coronary heart disease, then why oh why is there a need for a “replacement choice” when the saturated-fat-will-kill-you-deader-than-Minnesota-Dentist-Walter Palmer hypothesis is based on unsubstantiated nonsense?
Most disturbing is his recommendation to substitute “high-fat or processed meats and donuts” with “vegetable oils” and “whole grains,” with I assume the latter referring to whole wheat and the former to “heart healthy” oils like soybean, corn or safflower.
There are many other healthy alternatives to eating processed meats (or processed anything for that matter) and donuts that don’t include omega 6 fats and gluten grains.
So what seemed on the surface to be a welcome departure from failed nutritional dogma instead reveals itself to be the same old same old. I cannot in good conscience let this pass unanswered, which is why I’ve chosen to blog about a study published just this past month.
Now let me first preface my reporting by saying that I’m more than aware that it’s a mouse study and that rodents are not just like humans but with the addition of whiskers and a tail. And no, dressing them up in cute little outfits for poses in front your smartphone camera doesn’t change a blessed thing.
It’s always somewhat of a dicey proposition extrapolating results seen in a rodent study to us, although a good number of now validated hypotheses concerning human nutrition can be directly traced to this type of study.
So for the sake of scientific accuracy I must state that more research needs to be conducted in humans to verify that what happened to the animals in the following paper is relevant to us. That said, the results are entirely consistent with what I’ve written concerning the chemical composition of these commonly consumed fats and how they react in biological systems under varying levels of oxidative stress.
OK, enough with the disclaimers.
Let’s dive in to today’s research paper titled: Soybean Oil is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver. This is an open source PLOS one paper so feel free to download the original by clicking on the link.
Five sets of C57/BL6 male mice were divided into five groups. One group served as the control and mice in this group were fed a low-fat, high-fiber chow abbreviated as Viv.
The remaining four groups were each fed an isocaloric (having similar caloric value) high-fat chow with the following compositions: 1) A high-fat diet (HFD) consisting of 40% fat made up of 36% saturated coconut oil and 4% omega 6 polyunsaturated (PUFA) soybean oil with the latter added to provide essential linoleic acid. 2) A high-fat soybean oil diet (SO-HFD) again consisting of 40% fat but this time containing 21% coconut oil and 19% soybean oil. Diets 3) and 4) respectively were the same high fat diets but with approximately 26% of total calories coming from added fructose: a fructose-high-fat diet (F-HFD) and a fructose-high-fat soybean oil diet (F-SO-HFD). All diets had the same proportions of carbohydrate and protein.
Do keep in mind that the so-called high-fat soybean oil chow isn’t as high in omega 6 PUFA as I would like to see. It’s still composed of 21% coconut oil, which as a saturated fat would make this mixture less prone to oxidation and lipid peroxidation reactions than would be the case if the chow contained 40% soybean oil. In other words, the results you’re about to read in regards to soybean oil consumption would be more pronounced were coconut oil entirely absent from this high-fat formula.
And permit me to highlight one other thing about this study. Unlike most rodent studies that purport to demonstrate the inherent “suckitude” of saturated fat for rodent health and by extension human health, these researchers were quite cognizant of the fact that using lard as a stand-in for saturated fat is fraught with scientific peril.
As I’ve said formerly, the use of lard is a convenient way to muddy the results of health and nutrition research. It is the preferred mechanism for masquerading confirmation bias against saturated fat in nutrition studies done in rodents.
Every fat consumed by humans is composed of varying types of fatty acids. The accepted convention is to name a fat by the predominant fatty acid type that composes it.
The largest fatty acid component of lard is oleic acid, not saturated fat. This is the same fatty acid that makes up the majority of olive oil. Nonetheless, lard is always incorrectly referred to as a saturated fat in many published research papers. I’ve read way too many of these to believe this is just a mere oversight.
But it gets worse. The fatty acid composition of lard reflects what the pig ate. In this age of industrial factory farming, hogs are fed large amounts of grain high in polyunsaturated omega 6 fatty acids making the actual PUFA content of lard higher than many researchers let on.
Thus it was with great joy and personal vindication that I read the following:
“Coconut oil, which consists mainly of saturated fats of chain length 12 to 18, was used as the primary source of fat as it is naturally low in LA [linoleic acid] and other PUFAs, whereas diets made from lard (which is typically used in rodent studies) can have variable amounts of PUFAs depending on what the animals have been fed. Therefore, the use of coconut oil allowed us to study the metabolic effects of soybean oil in a saturated fat background, without affecting the final PUFA concentrations.”
Imagine that. Scientific integrity in the field of nutrition research.
So what, dear and ever-so-patient reader, were the results of said experiment?
Well, let’s start in the upper left-hand chart. This tracks weight gain in the mice fed the low-fat, high fiber diet (Viv), the high-fat coconut oil diet (HFD) and the high-fat soybean oil diet (SO-HFD). Not surprisingly, the low-fat, high-fiber diet resulted in the least weight gain because calories do ultimately matter as does feeding beneficial bacteria their preferred food source, i.e. fiber, to keep these beneficial organisms healthy and the liver free from the onslaught of chronic endotoxemia.
While both groups of mice fed the high-fat diet gained more weight, they did not gain the same amount. The largest weight gain was seen in the high-fat soybean oil group exceeding both the low-fat, high-fiber group and the high-fat coconut oil group.
This cannot be explained by food intake as there was no significant difference in food consumption between high-fat groups. I can only speculate that the mice who gained the most weight moved less and experienced depressed metabolism. And this, in turn, was most likely the result of chronic immune activation coupled with compensatory cortisol release/generation, but I digress.
In the upper right-hand chart, the addition of fructose to the coconut oil high-fat diet did not help matters any. Weight gain was higher in this group.
But even a mouse fed a high-fat coconut oil chow with added fructose gained less weight than a mouse fed high-fat soybean oil lacking fructose as seen in chart B1. What is somewhat curious is that graph B2 shows that the addition of fructose to the soybean oil diet actually caused less weight gain than eating the high-fat soybean oil chow sans fructose. This anomaly correlated with another interesting finding that I’ll get to in a bit.
Chart C1 shows that despite which high-fat diet fructose was added to, weight gain was similar over time. So the addition of fructose to fat appears to work synergistically to pack on the pounds, or grams in this case.
Figure C2 examines fat gain in various body parts depending on diet eaten. Soybean oil fed mice gained the most mesenteric, renal and subcutaneous fat of any of the groups studied.
Another interesting finding was that intestinal length was shorter in the rodents fed high-fat diets regardless of composition. The small intestine in all four high-fat mouse groups was shorter than in the mice fed the low-fat, high-fiber diet. So too the colon, although not significantly in those eating added fructose.
These processed high-fat rodent chows are effectively devoid of fermentable fiber and would therefore be deficient in the substrates needed by gut bacteria to thrive, not to mention produce the short-chain fatty acid butyrate. Besides being necessary for maintaining the blood-brain barrier, butyrate is also used to nourish and repair cells lining the digestive tract, which in turn ensures proper gut-barrier function and apparently intestinal length.
While none of this was investigated (gut flora was not studied in this paper), it likely accounts for why the intestinal tracts of the high-fat groups were appreciably different from the high-fiber controls.
One other interesting finding about the guts of these mice was that fructose feeding increased the occurrence of rectal prolapse. If you’re not sure what rectal prolapse is, be sure to click on the link to read all about this medical condition and marvel at the detailed drawings.
I admit ignorance as to why fructose intake would affect the structural integrity of the colon, but it did. The human incidence of rectal prolapse has increased significantly over the past few decades, and this study suggests that increased refined fructose consumption may be a major culprit behind this unfortunate phenomenon.
But most importantly of all, is the effect that soybean oil ingestion had on diabetes development, glucose tolerance and insulin resistance. After 20 weeks of eating a high-fat soybean oil diet, all mice developed diabetes. What’s even more surprising is that the mice fed the soybean oil diet but with added fructose were slightly less glucose intolerant than their litter mates.
None of the mice fed the high-fat coconut oil diet with or without fructose went on to develop diabetes, glucose intolerance or insulin resistance. To quote the researchers:
“All told, these results indicate that a moderately high fat diet of coconut oil, either in the presence or absence of fructose, does not induce significant diabetic symptoms (elevated fasting blood glucose and glucose intolerance) while isocaloric diets with soybean oil (either with or without fructose) do. Counter intuitively, our results also suggest that the addition of fructose to the diet may even protect against the IR [insulin resistance] caused by soybean oil.”
The bad news for rodents consuming soybean oil chow didn’t end here, however. While fructose has been shown in this and other studies to increase fat accumulation in the liver, eating chow high in soybean oil led to the development of extensive fat deposits and the ballooning of liver cells suggesting organ damage. This mimics what I highlighted in my post PUFAs, Leaky Gut, Endotoxemia and the Liver:
Here we see cross sectional slides taken of the livers of these animals. Horizontal row one compares the livers of mice fed the low-fat, high-fiber diet with mice fed the high-fat, low-fiber coconut oil diet. While there is clearly an increase in fat accumulation in the latter, the results are far better than what follows.
Row two shows what happened when fructose was added to either high-fat diet. Here we note the higher accumulations of liver fat as evidenced by the accumulation of orange- and rose-colored blobs in both slides.
But things got much worse in the livers of mice fed the high-fat soybean oil diet as shown in row three. At week 16 you can begin to see the ballooning of liver cells that only continues to worsen by week 35. Many of these structures appear to be foam cells forming in response to immune activation.
Past studies have shown that feeding rodents high-fat omega 6 diets promotes gut dysbiosis. (3) Where there is gut dysbiosis there is always chronic inflammation at the gut wall and in the liver, as well as compromised intestinal barrier function.
But an intriguing mystery remains: why are the livers in row three so much worse than the livers of mice fed soybean oil with added fructose? Shouldn’t the addition of fructose to a high-fat omega 6 PUFA diet make things appreciably worse? And why, as we read earlier, would glucose tolerance be somewhat improved with the addition of fructose?
While the researchers offer no explanation for this anomaly in their paper, I”ll offer you my two cents worth.
Fructose ingestion in excess of caloric expenditure is rapidly converted in the liver to oleic acid (a monounsaturated fat) by a process known as hepatic de novo lipogenesis. (4) Monounsaturated fatty acids being far more stable than polyunsaturated fatty acids offer a level of protection because these fats are less likely to undergo free radical damage from oxidative reactions caused by immune activation. Moreover, monounsaturates are incapable of generating toxic lipid peroxidation byproducts that not only damage cellular components but also screw with RNA and DNA synthesis.
According to Dr. Ray Peat, fructose also has a number of actions that may protect cells under oxidative stress. It is known to increase cellular respiration thereby countering suppression of mitochondrial function by lipid peroxidation. Accelerated metabolism would result in more rapid liver cell turnover and clearance of damaged cells. (5)
Fructose also rapidly increases uric acid production via the breakdown of adenosine triphosphate (ATP). (6) Uric acid is a powerful endogenous antioxidant that would counter the oxidizing and lipid peroxidation effects of excess omega 6 metabolism.
Finally 1,6-bisphospate a metabolite of fructose, binds to iron preventing the production of free radicals. (7)
While a liver full of fat is never ideal, this study suggests that fructose offers important antioxidant advantages in the presence of high omega 6 PUFA intake.
As I explained in my cortisol series, cortisol production, and especially its intracellular generation, typically occurs in direct proportion to inflammatory immune responses and is mainly mediated by activation of the cortisol/cortisone shunt via up-regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 2.
The higher the level of immune activation—in this case as a direct result of translocating gut bacteria, oxidative stress, lipid peroxidation toxicity and depleted antioxidant pathways—the higher the level of cellular cortisol all other things being equal. And the higher the level of intracellular cortisol, the more insulin resistant liver cells become.
What we are seeing here is the higher destructive force of polyunsaturated fat when incorporated into hepatic cells. Try to remember that the next time you’re casually walking down the cooking oil aisle of your neighborhood grocery store and spot an American Heart Association “Heart Check Mark” on a bottle of vegetable oil.
The irony is that if these findings hold true for humans, and I believe they will, the admonition to reduce fructose intake (i.e. sugar) without a simultaneous decrease in omega 6 PUFA consumption may actually be doing more harm than good! As the saying goes, the road to hell is paved with good intentions.
A considerable portion of this paper was devoted to studying the effects of these different diets on gene expression, specifically gene expression in the liver. I won’t go into the nitty-gritty of all this as it would extend this post well past the length I intended.
Suffice it to say that the high-fat soybean oil diet dysregulated gene expression in the liver of animals fed this “Heart Healthy” Frankenfood. Here are some highlights:
- Up-regulation of the Pdk4 gene. The increased activity of this gene is known to inhibit the pyruvate dehydrogenase complex in the citric acid cycle (aka the tricarboxylic acid (TCA) cycle or the Krebs cycle). Repression of this complex shifts the cellular balance of liver cells towards the runaway production of glucose.
- Up-regulation of several cancer-promoting genes, in particular Ctgf, H19, Mmp12, Mybl1 and Vnn1.
- At least 30 genes of the Cyp family involved in liver metabolism (the cytochrome P450 complex) were found to be impaired in the mice fed the high-fat soybean oil diet. These genes are mainly involved in the metabolism of linoleic acid, arachidonic acid, steroids, conversion of cholesterol to bile and detoxification of external agents like drugs, heavy metals and other xenobiotics.
One particular gene in the Cyp family—Cyp46a1—was dramatically up-regulated as well. This gene is involved in cholesterol metabolism and is assumed by these researchers to be the main causative agent in the well-known cholesterol-lowering effects of consuming vegetable oils. This is the physiological reaction that makes the tickers of American Heart Association board members thump, thump, thump with unmitigated joy.
While this genetic up-regulation is undoubtedly true, I seriously doubt that this is the entire story.
PUFAs and their lipid peroxidation byproducts suppress cellular respiration by impairing mitochondrial function. Impaired mitochondrial function would inevitably result in reduced cholesterol production.
As the liver is the largest producer of endogenous cholesterol, this would be reflected by a reduction in cholesterol output. How anyone could view this as net positive is beyond me.
Now I would be remiss if I failed to mention that the mice fed the high-fat coconut oil diet also showed an abnormality apart from shortened bowel length, namely an increase in spleen weight. The spleen is part of the immune system and its growth suggests chronic immune activation in these animals.
I think this anomaly can be best explained by the lack of fiber in all the high-fat diets, including the high-fat coconut oil chow. Fiber, particularly prebiotic fiber, is utilized by beneficial gut flora in the colon as a food source. Starve gut flora of their preferred food and several bad things begin to happen.
First, you end up with fewer and less diverse beneficial gut bacteria. The fewer beneficial bacteria, the more likely is the growth of opportunistic intestinal pathogens and the higher the risk of gut dysbiosis, increased intestinal permeability and endotoxemia.
Secondly, prebiotic fibers are fermented to produce essential short-chain saturated fatty acids with butyrate being particularly important for the health and integrity of the gut. Reduction in the number of butyrate producing bacteria will lead inevitably to gut dysfunction.
Clearly these high-fat, low-fiber diets increase endotoxin translocation. But even with little fiber in the diet, this study clearly demonstrates that the type of fat consumed makes a huge difference when endotoxemia and chronic inflammation are part of the mix.
The deleterious effects of a bad diet can be somewhat mitigated by maintaining a healthy and diverse gut flora through the introduction of prebiotics and probiotics either via food or supplements to the diet. Nevertheless, no supplement(s) can entirely compensate for unhealthy eating habits and that includes consuming copious quantities of omega 6 vegetable oils.
Now I cautioned that we need to be careful when deriving dietary recommendations or admonitions from animal studies. Nonetheless, given the nature of PUFAs I take these results quite seriously and recommend you do the same.
In the past I’ve spent a great deal of time explaining the chemistry of fatty acids and why polyunsaturated fats are the most unstable fats of all and therefore the riskiest when consumed in excess. The laws of chemistry do not become suddenly inoperative just because spokespeople for the edible oils industry or “Heart Check” bribe takers at the American Heart Association or financially-conflicted leaders of major nutritional organizations or an assistant professor of epidemiology choose to ignore them.
And that brings me back to professor de Souza. While I do welcome his contribution in burying the saturated fat-heart disease hypothesis, his regrettable advice that people should consider vegetable oils as a “healthy” alternative to unhealthy eating habits is so far off the mark as to strike me as utterly surreal given the scientific findings I’ve spent years bringing to your attention.
Not that I’m surprised, mind you. But I do confess to an encroaching weariness at having to sound the alarm against nutritional recommendations made by people who given their training, credentials and position ought to know better.
Unless someone can explain to me how ingesting excessive quantities of these highly unstable processed fats in their “natural” non-trans chemical state is healthy for humans (and their pets) contrary to what we see demonstrated in well-designed rodent studies and in often ignored human investigations like the Rose corn oil study (8) or the Sydney Diet Heart Study (9), then my advice remains as before: keep your intake of these fats to an absolute minimum or else suffer the consequences of biological derangement and disease.
That, unfortunately, is easier said than done. According to the U.S. Department of Agriculture, soybeans are the second most planted crop in the United States eclipsed only by corn. (10)
It is by far the largest oilseed crop in the United States accounting for about 90 percent of all oilseed crop production, far exceeding cottonseed, sunflower seed, rapeseed and peanuts. Soybean oil is a very cheaply manufactured oil so it should be no surprise that it’s an ingredient in damn near all processed foods and very widely used in both fast-food and traditional sit-down restaurants.
If you check the food labels of prepared mayonnaises, bottled salad dressings, baked goods, frozen foods, sauces, margarines, potato chips, etc., more often than not you’ll see soybean oil or another equally noxious omega 6 vegetable oil staring back at you from the ingredients list.
Seed oil crops and the oils made from them are huge business for U.S. agriculture, processed human and pet food manufactures, supermarkets and corporate restaurant chains. The profits generated, as well as the influence that that money buys in the hallowed halls of academia, medicine, “non-profit” health associations, the corporate-owned media and government agencies guarantees that the misguided advice to eat these fats as part of a “healthy diet” will continue to be monotonously dispensed to an unsuspecting public for the foreseeable future.
To once again quote Upton Sinclair: “It is difficult to get a man to understand something, when his salary depends on his not understanding it.” I would add that it is doubly difficult when we’re talking about the profit interests of large transnational corporations and their bought-and-paid-for “experts”, politicians and government bureaucrats who are ever so eager to do their bidding.
OK, I’ve said my piece.
Until next time.