1. Introduction: What are healthy fats?
2. Breaking down the different types of fats
3. Polyunsaturated fatty acids are essential
4. Omega 3 vs Omega 6 fatty acids
5. Competition between omega-3s and omega-6s in the diet
6. Amounts of fatty acids in the immune system
7. How the fatty acids in immune cells effects their function
8. What happens when there are more omega-3s than omega-6s in the immune cells?
9. Dietary effects of omega-3 fatty acids on inflammation
10. Studies using fish oil on inflammation and immune function
11. Fish oil and allergic diseases
12. Conclusion
Introduction: What are healthy fats?
What fat sources are heatlhy?! If you have been around the nutrition community, you might have heard about the benefits of olive oil and how that can be classified as a healthy fat. But we have so many more choices! What about coconut oil, vegetable oil, margarine, butter, lard, or soybean oil? What's the difference between them, which are good and which are bad? Those are the questions that we will begin to tackle with this blog.
Breaking down the different types of fats
To make things simple, lets classify fats into two main categories: saturated and unsaturated fats. A fat is just a long chain of carbon with hydrogen atoms bonded to it. It might look kind of like a centipede or something like that lol. The little legs are the hydrogen and the body is carbons. All that "saturated" means is that the carbon chain is holding the maximum amount of hydrogen atoms that can fit on the carbon chain. It's like a centipede having all of its legs. "Unsaturated" means that it is not holding the maximum number of hydrogen atoms, hence, it is not saturated in hydrogen, making it "unsaturated." This is like a centipede who lost some of his legs. When a fat is missing hydrogen, it has to form a double bond at the place where the hydrogen is missing. That's just the way it works. So, unsaturated fats have double bonds present in their carbon chains, whereas saturated fats do not. Sorry about the centipede reference, I am done now.
Why do any of these hydrogen atoms or double bonds even matter? It's actually quite simple. When you change the configuration (shape) of the fat, you give it different properties. That's all. So, depending on where the double bonds and hydrogen atoms are, the fat could either be solid or liquid at room temperature, it might start to breakdown at 350 degrees in the oven instead of 400, or it might confer different functions in your body for energy utilization or for the health of your cells, all depending on how it is made. So, to make the long story short, different fat molecules have different properties and as a result will have different functions in your body when you eat them!
Now that we've got that taken care of, we are going to focus on unsaturated fats. We can break down unsaturated fats into two groups: monounsaturated fats (MUFA) and polyunsaturated fats (PUFA). The word "mono" means one, and the word "poly" means many. As you may be able to guess, a mono-unsaturated fat has one double bond where it is missing a hydrogen atom, and poly-unsaturated fats have multiple double bonds where they are missing multiple hydrogen atoms. Phew, that was a "fat" discussion lol (pun intended!).
Polyunsaturated fatty acids are essential
So, I have bored you up until now to set the context for all of the juicy stuff to follow because I am going to be talking about poly-unsaturated fats and their role in the human diet! I figured that it was beneficial to get an overview of the different types of fats and broad classifications before diving into a particular subset. So let's get after it now!
Polyunsaturated fatty acids cannot be made in our bodies like saturated or monounsaturated fatty acids. We lack the ability to do this because we are missing the right enzymes (machinery that converts one molecule to another). Plants have these enzymes and can make polyunsaturated fatty acids (1). As a result of us not being able to make these fatty acids, we call them "essential fatty acids" (1). They are essential because we must consume them in our diet in order to be healthy!
Omega 3 vs Omega 6 fatty acids
Now, we need to clear up the difference between omega 3 and omega 6 fatty acids. You've probably heard fish oil being touted as having beneficial omega 3s before, and that would be correct. Remember how in the introduction the different names of the fats said something about their structure and function? The same thing applies here. Omega-3 just means that the double bond is only 3 bonds away from the end of the fat chain, where omega-6 means the double bond is 6 bonds away from the end of the fat chain. To put things in centipede terms, an omega 3 fat is missing the third to last leg on one side, and an omega-6 centipede is missing the 6th to last leg on one side lol! Sorry, I had to bring that reference back up. Now you won't forget it. As a result of having different bonds, they are metabolized (digested) differently and contribute to different functions in the body that you will see below.
Before we get much further, let me point out that there are multiple different omega-3 fatty acids. These are alpha-linoleic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). They all have a double bond 3 bonds away from the end of the fat chain as described above. Examples of omega-6 fatty acids are linoleic acid (LA) and arachidonic acid (AA), which both have double bonds 6 bonds away from the end of the fat chain as described above as well.
Competition between omega 3s and omega 6s in the diet
When we consume linoleic acid (an omega 6) in the diet, it is converted through several steps into a molecule called arachidonic acid (AA). Arachidonic acid is the main fatty acid responsible for triggering the inflammation and immunity pathway (1). Keep this in mind!
When we consume alpha-linoleic acid (an omega-3), this is able to be converted to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1). We can also consume EPA and DHA through our diets in foods like sardines and salmon.
Now, the interesting thing is that when we eat omega 6s (linoleic acid) or when we eat omega-3s (alpha-linoleic acid), they require the same enzymes (or machinery) to get broken down. This means that to turn linoleic acid into arachidonic acid it require the same tools and machinery that it takes to turn alpha-linoleic acid into EPA or DHA (1). Thus, we have competition folks!
Amounts of fatty acids in the immune system
Our immune system has lots of little cells that help protect and defend us. Some of these cells include lymphocytes, neutrophils, and monocytes (1). Regardless of what they are, they contain both omega 6 fatty acids (arachidonic acid) and omega-3 fatty acids (DHA & EPA). In animal studies, it has been shown that by increasing the amount of omega 3 fatty acids in the diet (by eating fish oil), this decreased the amount of omega 6 fatty acids and increased the amount of omega-3 fatty acids in the cells! (1). Competition indeed!
How the fatty acids in immune cells effects their function
An important concept in all of biology is that structure greatly affects function. Fish have fins that help them to swim. Monkeys have arms that help them swing from trees. Their structure determines the function that they are capable of. In the same way, the composition of fatty acids in your immune cells effects their function.
One thing that is effected by the fatty acids is the fluidity of the cell membranes (1). The cell membrane is just the outside of the cell, kind of like a beach ball. The cell membrane is the part of the beach ball that you don't want to pop, and everything inside the beach ball is like the inside of the cell.
Another thing that the fatty acids effect is cellular signaling. This just means how well the cell can receive messages from the outside environment. It's like the cell has a walky-talky and the fatty acids in the cell determine what channels it can pick up (1). This means that the immune system will respond differently to the messages that it receives depending on the fatty acids in the cell membrane (1).
A third function effected by the fatty acids in the cell membrane is the inflammatory response. Arachidonic acid is normally converted into molecules called eicosanoids which help initiate the inflammatory/immune response when needed, as well as the intensity and duration of the inflammation. Examples of eicosanoids include leukotrienes (LT) or prostaglandins (PG). By altering the availability of arachidonic acid (an omega-6), the level of the inflammatory/immune response will also change (1).
What happens when there are more omega 3s than omega 6s in the immune cells?
Okay, it's story time. You already heard that omega 6s like arachidonic acid are converted into molecules called eicosanoids, which include leukotrienes and prostaglandins. But what do they do? Prostaglandins for example, (an eicosanoid that is made from arachidonic acid), function in causing fever, dilating your vessels, as well as enhancing pain and swelling. Ah, so when you roll your ankle and you hear someone say it is "inflamed", what they are essentially saying is that these prostaglandins and leukotrienes, among others, initiated an immune response to help heal the damaged area. The result is that you have a red, achy, warm, and puffy ankle.
Arachidonic acid is capable of being converted into a plethora of different eicosanoids, one of which are prostaglandins that we mentioned earlier. Eicosanioids are able to effect all kinds of immune system cells and molecules like tumor necrosis factor (TNF-alpha), Interleukin-1 (IL-1), or intereferon-gamma (IF-gamma) (1). It's not necessary to know what these are or what they do, but just know that arachidonic acid is able to produce a lot of different eicosanoids that impart a wide range of functions in the inflammatory response, like when you roll your ankle or have a chronic inflammatory disease.
Dietary effects of omega-3 fatty acids on inflammation
Here's where things start to come together! Remember earlier when we talked about how the fats that we eat in our diet influence the fatty acids on the cell membrane (beach ball analogy) and therefore effect the function of the immune cells? Well, when we eat omega-3 fatty acids like DHA or EPA, we decrease the amount of arachidonic acid in the membranes of these immune cells (1). Remember the competition argument?!This means that less of the eicosanoids that we just talked about in the section above will be produced from arachidonic acid. Here's the kicker. You know how arachidonic acid is converted into eicosanoids like prostaglandin or leukotrienes? Well, omega-3s like EPA can be converted the same way into prostaglandins or leukotrienes, BUT these eicosanoids are just slightly different than those produced by arachidonic acid. They are still prostaglandins and leukotrienes, but they are slightly different depending on whether they were made from arachidonic acid or from EPA, and this makes all the difference!
So, this means that more of the prostaglandins and leukotrienes have originated from EPA in the cell. It turns out that the eicosanoids derived from EPA are less potent than those produced from arachidonic acid and this influences the nature and strength of the inflammation that occurs (1). What this means is that by eating more omega-3s in the form of EPA and DHA as opposed to omega-6s like linoleic acid, this can lead to less inflammation and better immune function (1). Let's pretend you roll your ankle again but have been crushing the salmon fillets recently. Your inflammatory response might not be as bad (not as puffy, red, achy) as someone who has been slamming down french fries and ranch dressing.
Studies using fish oil on inflammation and immune function
There has undoubtedly been a range of results published on the ways that fish oil effect the inflammatory process (1). In lab animal studies, fish oil consumption decreased the amount of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-alpha), Intenleukon-1beta (IL-1B), and Interleukon-6 (IL-6), IL-2, and IFN-gamma, all molecules associated with inflammation (1). When given fish oil after being injected with endotoxins (harmful toxic substances from bacteria) or after sustaining burns, those given the fish oil had lower concentrations of some of these inflammatory molecules, highlighting the anti-inflammatory capabilities of fish oil (1).
Human studies have demonstrated the anti-inflammatory effects of fish oil as well. Supplementing with more than 2.3g of EPA and DHA per day has been shown to decrease superoxide production, and decrease TNF, IL-1, IL-2, IL-6, IFN-gamma, and decrease lymphocyte proliferation (1).
Fish oil has been shown to significantly increase survival after being exposed to lipopolysaccharides which are a form of endotoxin (a toxic part of certain bacteria) (1).
There are many inflammatory chronic diseases like inflammatory bowel disease (chron's disease), rheumatoid arthritis, psoriasis, and multiple sclerosis. Fish oil has been shown to promote anti-inflammatory effects (lowered LTB4, IL-1, and CRP (a general marker for inflammation) in some of these conditions. Furthermore, placebo-controlled, double-blind trials with fish oil use for chronic inflammatory disease demonstrate improvement of disease state and less use of anti-inflammatory medications with the strongest evidence being for rheumatoid arthritis (1).
Some studies using a lower, or more modest amount of fish oil reported no effect on inflammatory or immune function (1). It is speculated that discrepancies in experimental protocols, cell cultures, and assays are thought to explain the discrepancies observed, although a solid body of evidence now supports the anti-inflammatory capabilities of fish oil in the human diet (1).
Fish oil and allergic diseases
Let's talk about asthma for a second. The eicosanoids made from arachidonic acid play a role in the bronchoconstriction (what makes your airway narrow making it harder to breath) that is present in asthma. Because omega 3s are known to decrease the amount of eicosanoids derived from arachidonic acid, fish oil has been experimented with in asthma patients. The studies are mixed, but some have demonstrated significant improvements in symptoms (1). High omega-3 unsaturated fatty acid intake helped greater than 40% of subjects improve lung function, although some subject's conditions actually worsened (1).
Conclusion:
Fats can be generalized into two classifications for our purposes: saturated and unsaturated. Of the unsaturated fatty acids, we can further break them down into monounsaturated and polyunsaturated fatty acids. Of the polyunsaturated fats, we can break these down into omega 3 fats (alpha-linoleic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)) and omega6 fats (linoleic acid). Both omega 3s and omega 6s can be deposited in the membranes (the outer layer) of our immune system cells. Because omega 3 and omega 6 fats use the same enzymes to be broken down into the molecules that initiate immune responses, they can be said to compete with one another. With this being said, the more omega 6s we eat, the more omega 6 immune system byproducts we will have. Conversely, the more omega 3s that we eat, the more omega 3 byproduct we will have. The amount of omega 3 or omega 6 greatly influences the function of the immune system cells like the fluidity of the cell membranes, their ability to communicate, and the extent of the inflammatory response. It turns out that omega 3 byproducts have more of an anti-inflammatory effect compared to their omega 6 counterparts. With this being said, they are considered anti-inflammatory. Studies using fish oil, a source of omega 3 have been shown to decrease many of the inflammatory molecules like TNF-alpha and IL-6. Human studies have also demonstrated a reduction in inflammatory molecules with fish oil use. Fish oil has also been postulated as helping decrease the inflammatory response in chronic inflammatory diseases like Chron's and Rheumatoid arthritis, as well as allergic diseases like asthma. Despite mixed results, there is a solid body of research suggesting the anti-inflammatory effects of fish oil (omega 3s) in humans (1).
1. Calder, PC and Grimble RF. 2002. Polyunsaturated fatty acids, inflammation and immunity. European Journal of Clinical Nutrition. 56(3):S14-S19.
2. Simopoulos, A.P. 2002. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy. 56(8): 365-379.
3. Simopoulos, Artemis P. 2016. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients. 8(3): 128.
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