This is a short post about an intriguing study done in rodents to assess what effect different polyunsaturated fatty acids (PUFAs) have on progression of ulcerative colitis (UC). (1) Ulcerative colitis is defined by Taber’s medical dictionary as:
“An inflammatory bowel disease marked pathologically by continuous inflammation of the intestinal mucosa, which typically involves the anus, rectum, and distal colon, and sometimes affects the entire large intestine. It occurs most often in patients during the second or third decade of life, although a second cluster of cases occurs in patients in their sixties. The disease is associated with an increased incidence of cancer of the colon.
SYMPTOMS: Bloody diarrhea and pain with the passage of stools are characteristic. In severe cases, patients may have more than 6 bloody bowel movements in a day. Iron deficiency anemia often develops as a result.”
Common drugs to treat UC are sulfasalazine (Azulfidine) and 5-aminosalicylate drugs (Asacol, Delzicol, Asacol HD, Pentasa, Salofalk, Dipentum, Colazal, Apriso and Lialda). These are anti-inflammatory drugs and are often used with corticosteroids to reduce symptom severity. In intractable cases, it’s not unusual for physicians to recommend a colectomy, i.e. removal of the colon.
There has long been a suspicion that diets rich in fat, but especially omega 6 fats (corn, safflower, soybean, sunflower, walnut, sesame, grape seed and cottonseed oils) contributes to development of UC in humans. (2) Given what I wrote in my post on polyunsaturated fats, this doesn’t surprise me in the least. The hope remains, however, that supplementing with omega 3 fats can reverse the disease.
To that end, the researchers in today’s paper divided mice into three groups. (3) The first was a low-fat control group that derived only 9% of their calories from corn oil.
A second and third group were fed a very high fat diet where 40% of calories were derived from this macronutrient. These chows contained 20% total PUFAs.
Group two, or the high omega-6 PUFA group, derived the overwhelming majority of their fat from corn oil. The third group ate 1% less corn oil because fish oil was substituted instead.
The colons of these mice were then infected with gram-negative Citrobacter rodentium (C. rodentium) to induce UC.
These graphs record the blooming of three pathogenic strains in the intestines of these mice after introduction of the bacteria. The first bar in each graph is the control or low omega 6 PUFA oil group. The second the group fed high levels of omega 6 corn oil exclusively, and the last bar represents the group fed corn oil, but with added omega 3 fish oil.
The increase in pathogenic strains was quite dramatic in the high (“heart-healthy”) omega 6 PUFA group. These fats caused lots of inflammation during infection along with damage to cells lining the colon.
And yet, if you go to the American Heart Association website, you’ll read this tidbit of ‘helpful’ advice:
“Choose: Vegetable oils and margarines with liquid vegetable oil as the first listed ingredient. Examples are canola, corn, olive, peanut, safflower, sesame, soybean and sunflower oils.”
No mention of bloody diarrhea or gut dysbiosis on that website, no siree!
With the exception of olive oil, these oils are all high in omega 6 linoleic acid and apparently wonderful at contributing to gut dysbiosis.
But I digress.
So, dousing the insides of these mice with fats known to increase oxidative stress and lipid peroxidation in cells lining the gut wall, did what anyone who didn’t fall asleep reading my PUFA post would have predicted.
But clearly the mice fed fish oil fared better. As you see, levels of the three pathogenic strains were significantly lower than in the group fed the high omega 6 PUFA chow. Not only that, but colonies of beneficial lactobacillus and bifidobacteria were also significantly higher than in either the control or omega 6 group.
So Ray, I guess this is your way of backtracking from warning against supplementing with omega 3s during episodes of intestinal dysbiosis, right?
Not quite my cheeky little blog reader, and here’s why:
This graph shows survival rates after infection for each group. The top line represents those mice fed either the low or high omega 6 PUFA diet (The triangles are superimposed on the squares, which is why you don’t see a separate line for the high omega 6 PUFA group). The lower line represents rodents who ate the high omega 6 chow supplemented with omega 3 fish oil.
What we see here is that 100% of the mice on either the low or high omega 6 diet survived ten days after being infected with C. rodentium. But what you also see here is that the mice supplemented with fish oil experienced a 30% mortality rate by day eight post infection. I’ll explain why in a bit.
This chart tracks changes in starting and ending body weights. The low and high omega 6 groups pretty much ended at the same weight after ten days of colitis. Not so the mice also fed omega 3s. They experienced significant weight loss.
While this may on the face of it appear to be a good thing, the reason these mice lost weight was due to cachexia. For those of you unfamiliar with cachexia, I refer you to this post.
So why the deaths? Because as I explained in my post on PUFAs, omega 3s cause the death or apoptosis of certain subtypes of immune cells. This immune suppressing (aka: anti-inflammatory) action of omega 3s has consequences, and in this particular case that consequence was sepsis.
Sepsis is whole-body inflammation caused by a systemic infection. Pathogenic organisms like the C. rodentium given these rodents to induce colitis, as well as mycobacteria, fungi, protozoa and viruses can all initiate an inflammatory cascade that may result in death.
This is a somewhat curious finding because the omega 3 supplemented group was far better able at keeping C. rodentium confined to the gut lumen. In other words, they had less gut leakiness than the high omega 6 group. And not only that, their colitis was milder.
Nevertheless, supplementing with omega 3 caused immune suppression. This immune suppression meant that these rodents were either handicapped when it came to eliminating the infection or preventing it from becoming systemic should any of the bacteria breach the gut wall, which it clearly did in some of the mice.
As these researchers put it:
“While C. rodentium-induced inflammation promotes colonic damage in C57BL/6 mice…, these responses are also important for C. rodentium clearance… Our results suggest that ω-3 PUFA supplementation to an ω-6 PUFA rich diet results in a milder colitis but impairs infection-induced inflammatory responses important for preventing systemic C. rodentium infection. Similarly, another study demonstrated that mice fed high levels of ω-3 PUFAs had impaired immune function and could not produce a response against Helicobacter hepaticus– induced infection… Consumption of ω-3 PUFA rich diets may have anti-inflammatory properties however this may prevent the body from mounting appropriate immune responses critical for host defense.”
In these animals, immune suppression resulted in an inability to clear lipopolysaccharides (LPSs) derived from gram-negative C. rodentium. And one reason for this is that omega 3s suppress expression of a particular cell type that produces intestinal alkaline phosphatase (IAP). IAP detoxifies LPSs.
And because these mice couldn’t detoxify LPSs, they were particularly susceptible to acquiring sepsis. This was clear by an increased amount of LPS binding protein (LBP) in their blood serum.
As I wrote in my PUFA post, a major concern in using omega 3s to treat gut dysbiosis is the increased risk of unbalancing the immune system away from a Th1 response towards Th2 dominant immune activation. One of the common outcomes of doing so is to depress Th1 defenses against bacterial, fungal and viral infections. This can be a dangerous proposition, especially when harmful bacteria breaches the gut wall.
Levels of the cytokines interleukin 15 (IL-15) and our dear old friend tumor necrosis factor alpha (TNF-α) were also higher in these rodents. It was elevations of the latter that no doubt accounted for the observed weight loss.
I also suspect that the high omega 6 intake in this group further compromised these animals by reducing total serum cholesterol levels. It is, after all, this ability of omega 6 vegetable oils to consistently lower blood lipid levels that causes male board members of the American Heart Association to pop boners whenever recommending these fats to a gullible public.
But as I’ve written before, all lipoproteins, including very low density (VLDL), low density (LDL) and high density lipoproteins (HDL), bind to and inactivate LPSs. (4) This is one reason for the results of the Kaiser Permanente Cholesterol study.
How relevant are the results of this paper for humans? Well, I trust none of you are eating purified rodent diets, or at least I hope not.
That said, this is yet another study showing that dietary PUFAs in large amounts are not your gut’s best friend. In the case of omega 6s, these fats both before and after infection are known to cause gut dysbiosis, induce pro-inflammatory responses and contribute to liver damage.
In the case of supplementing with omega 3s, their anti-inflammatory effects are due entirely to their ability to suppress certain immune responses. But this brings up some interesting questions.
Are people out there increasing their risk of chronic, unresolved gut infections by ingesting these fats on a daily basis? Is this a major reason many people relapse after being successfully treated for small intestinal fungal and bacteria overgrowth? Are some people being hospitalized with sepsis because of this “Great Fish Oil Experiment“? I honestly don’t know, but the outcomes of this and other rodent studies concern me greatly.
These results are eye-opening in that the quantity of omega 3 fed to these mice followed guidelines set forth by my dear, dear friends at the American Heart Association (AHA). These recommendations are for .5 to 1.8 grams of long-chain omega 3 PUFAs daily for humans. Adjusted for the body weight of these mice, that meant adding just 1% of these fats to their 19% omega 6 PUFA total.
Now to be fair, the AHA also recommends eating seafood to get your omega 3s, and I wholeheartedly agree. As I’ve mentioned before, getting your omega 3s this way ensures that you are also getting selenium. This trace element helps generate glutathione, your body’s master antioxidant.
But let’s face facts. Not everyone is getting their omega 3s by eating seafood. Way too many Americans are marinating their insides with cod liver oil, krill oil or fish oil capsules often bought from Amazon, Walmart, Target or Costco.
As a result, a lot of these folks are inadvertently handicapping their immune response to any intestinal infections they may acquire via food or other means. Supplementing with these fats also makes resolving gut dysbiosis very difficult no matter how many probiotics, fermented foods, resistant starch, prebiotics, antibiotics or anti-fungals these people may take to treat the problem.
So yes, omega 3s do increase the level of beneficial bacteria in the colon, namely by tamping down inflammation. As you all know by now, healthy colonies of beneficial bacteria and inflammation don’t mix.
However, the hazards of immune suppression should not be taken lightly, otherwise you risk being part of the following conversation:
Doctor: We’ve cured your husband.
Wife: But he’s dead!!!
Doctor: Yes, but before he died his ulcerative colitis was in remission so the therapy was a resounding success!
What this study makes clear is that you can’t compensate eating crap loads of omega 6 PUFAs by adding omega 3 supplements without experiencing some level of immune suppression and the consequences that flow from that. The only long-term healthy option when it comes to gut health and fat is to radically cut your omega 6 PUFA intake.
This means eating real food, and getting the majority of your fats from saturated and/or monounsaturated sources. This will, however, be all but impossible to achieve if most of your food comes out of a bag, box or drive-through window just so you know.
For those of you battling any form of gut dysbiosis, including Crohn’s disease or ulcerative colitis, I again caution you from taking omega 3 supplements as a way to resolve your issues.