Does Linoleic Acid cause Inflammation?

The effects of linoleic acid on the human body are largely dependent on genes, a new study from the University of Eastern Finland shows. Linoleic acid is an essential fatty acid. People carrying different variants of the FADS1 gene had a different inflammatory response and different changes in their fasting glucose levels when supplementing their diet by linoleic acid rich sunflower oil. This was the first time these associations were studied in humans.

According to Postdoctoral Researcher Maria Lankinen from the University of Eastern Finland, the findings warrant speculation on whether the recommended intake of linoleic acid -- and possibly other fatty acids, too -- should be tailored to match a person's genes.

"However, further research is needed before we can make any recommendations based on genes," Postdoctoral Researcher Lankinen says.

The FADS1 gene regulates the body's fatty acid metabolism and also plays a role in glucose metabolism. A person's diet, in turn, has a major impact on the concentrations of different fatty acids in the body. Linoleic acid is found in plant-based oils, nuts and seeds, and it is the most common polyunsaturated omega 6 fatty acid. A high intake and high levels of linoleic acid in the blood have been associated with a reduced risk of type 2 diabetes and cardiovascular disease. On the other hand, however, the metabolites of linoleic acid can mediate inflammation, which is why a high intake of linoleic acid is regarded as a plausible factor contributing to low-grade inflammatory state. According to the newly published study, these contradictory observations could be explained by genetic differences.

The study explored whether point mutations in rs174550 of the FADS1 gene modify the effects of linoleic acid on serum fatty acid composition and on fasting glucose, insulin and CRP levels. These were analysed in more than 1,300 middle-aged men participating in the METSIM (Metabolic Syndrome in Men) Study. In addition, 60 men participated in the FADSDIET intervention for carriers of two different gene variants. Over the course of four weeks, they supplemented their daily diet by 30-50 ml of linoleic acid rich sunflower oil. Selecting the participants on the basis of their genes makes this a unique research setting, which provides information on the interactions of diet with genes.

The findings indicate that the effects of linoleic acid on the human body are largely dependent on which variant of the FADS1 gene a person is carrying. This has an effect on, for example, how effectively a linoleic acid supplement can lower fasting glucose levels. Moreover, depending on the gene variant, increased intake of linoleic acid can make a person's CRP levels go either up or down. The FADS1 gene variant also had an effect on the levels of inflammation mediators, which are created from the metabolites of linoleic acid and other omega 6 fatty acids.

The study was conducted in collaboration with Karolinska Institutet, and the findings were published in the American Journal of Clinical Nutrition (2019).

linoleic acid foods

Related: Best anti inflammatory supplements

Avoiding Omega-6 Fats Is Key for Good Health

While considered an essential fat, when consumed in excessive amounts, which over 99% of people do, LA (an omega-6 polyunsaturated fat or PUFA) acts as a metabolic poison.

Most clinicians who value nutritional interventions to optimize health understand that vegetable oils, which are loaded with omega-6 PUFA, are something to be avoided. What most fail to appreciate is that even if you eliminate the vegetable oils and avoid them like the plague, you may still be missing the mark.

Chances are you're still getting too much of this dangerous fat from supposedly healthy food sources such as olive oil and chicken (which are fed LA-rich grains).

Another common mistake is to simply increase the amount of omega-3 that you eat. Many are now aware that the omega-3 to omega-6 ratio is very important, and should be about equal, but simply increasing omega-3 can be a dangerous strategy. You really need to minimize the omega-6. 

Linoleic Acid Is a Primary Contributor to Chronic Disease

When we talk about omega-6, we're really referring to LA. They're largely synonymous, as LA makes up the bulk — about 60% to 80% — of omega-6 and is the primary contributor to disease. Broadly speaking, there are three types of fats:

  • Saturated fats, which have a full complement of hydrogen atoms
  • Monounsaturated fats, which are missing a single hydrogen atom
  • PUFAs, which are missing multiple hydrogen atoms

The missing hydrogen atoms make PUFAs highly susceptible to oxidation, which means the fat breaks down into harmful metabolites. OXLAMS (oxidized LA metabolites) are what have a profoundly negative impact on human health. While excess sugar is certainly bad for your health and should be limited to 25 grams per day or less, it doesn't oxidize like LA does so it's nowhere near as damaging.

Over the last century, thanks to fatally flawed research suggesting saturated animal fat caused heart disease, the LA in the human diet has dramatically increased, from about 2 to 3 grams a day 150 years ago, to 30 or 40 grams a day. 

On a side note, do not confuse LA with conjugated linoleic acid (CLA). While most think CLA and LA are interchangeable, they're not. CLA has many potent health benefits and will not cause the problems that LA does.

How Excess Linoleic Acid Consumption Damages Your Health

At a molecular level, excess LA consumption damages your metabolism and impedes your body's ability to generate energy in your mitochondria. There is a particular fat only located in your mitochondria — most of it is found in the inner mitochondrial membrane — called cardiolipin.

Cardiolipin is made up of four fatty acids, unlike triglycerides which have three, but the individual fats can vary. Examples include LA, palmitic acid and the fatty acids found in fish oil, DHA and EPA. Each of these have a different effect on mitochondrial function, and depending on the organ, the mitochondria work better with particular kinds of fatty acids.

For example, your heart preferentially builds cardiolipin with LA, while your brain dislikes LA and preferentially builds cardiolipin in the mitochondria with fats like DHA. 

Oxidation of Cardiolipin Controls Autophagy

Oxidation of cardiolipin is one of the things that controls autophagy. In other words, it's one of the signals that your body uses when there's something wrong with a cell, triggering the destruction and rebuilding of that cell. Your cells know that they're broken when they have too many damaged mitochondria, and the process that controls this is largely the oxidation of omega-6 fats contained within cardiolipin.

Animals typically develop cancer once the LA in their diet reaches 4% to 10% of their energy intake, depending on the cancer.

So, by altering the composition of cardiolipin in your mitochondria to one that's richer in omega-6 fats, you make it far more susceptible to oxidative damage. Goodrich cites research showing that when the LA in cardiolipin is replaced with oleic acid, another fat found in olive oil, the cardiolipin molecules become highly resistant to oxidative damage.

"That is basically what I think we need to go back to," he says. "We evolved with low levels of LA in our diet and therefore in our cardiolipin. One of the neatest papers I've ever seen looking at this, something that encapsulated this whole model that I'm talking about, fed rats either a regular high carbohydrate diet, or they added PUFAs to their diet.

Just adding the omega-6 fats to the diet caused the mice to become diabetic. They became insulin resistant, leptin resistant, obese, and the differences are pretty stark between the fat mice and the skinny mice on the high carbohydrate rat diet …

The high-PUFA diet caused a breakdown in the cardiolipin content in the mitochondria in their hearts. So just adding seed oils caused heart damage through a change in the cardiolipin composition."

OXLAMS Trigger Cancer

Heart disease isn't the only condition triggered by excessive LA intake and the subsequent OXLAMS produced. It also plays a significant role in cancer. As noted by Goodrich, to induce cancer in animal models, you actually have to feed them seed oils. "So, this is a really fundamental process that we're talking about here," he says.

As I mentioned above, animals typically develop cancer once the LA in their diet reaches 4% to 10% of their energy intake, depending on the cancer. In the breast cancer model, cancer incidents increase once 4% of calories are in the form of seed oils.

4HNE is a mutagen, in other words, a toxin that causes DNA damage. One of the primary genes it damages is the P53 anticancer gene. Mutations in the P53 gene are found in 15% of cancers, making it one of the most common. 

On a side note, one of the major jobs of glutathione is to detoxify 4HNE. You can often tell that you have excess 4HNE if your glutathione levels are low, as this means it's being used up detoxifying 4HNE.

Increased Linoleic Acid Also Increases Your Risk of Sunburn

So, to summarize, the dramatic increase in LA — and the oxidative end products that cause the damage — is the primary cause behind the increase in chronic diseases such as obesity, diabetes, heart disease and cancer.

Simply lowering your LA intake to what your great-great grandparents used to eat, you can essentially eliminate almost every single one of the diseases that are now prematurely killing us.

Seed Oils Raise Risk of ARDS and COVID-19 

Considering the metabolic and mitochondrial damage caused by LA, there's reason to suspect LA may also play a role in COVID-19, as some white blood cells convert LA into leukotoxin. Essentially, LA contributes to the inflammation domino effect that eventually kills. 

Melanoma Linked to Linoleic Acid

study from 1987, during which samples of fat tissue were taken from 100 melanoma patients and 100 people without melanoma and analyzed for fatty acids.

Not only is there an increase in linoleic acid in the tissue of all the subjects, but the percentage of polyunsaturated fatty acids (PUFAs) is significantly higher in the melanoma patients’ tissue. “The suggestion is made that increased consumption of dietary polyunsaturates may have a contributory effect in the etiology of melanoma,” the researchers concluded.

Linoleic acid is the primary fat found in omega-6 polyunsaturated fats, including vegetable/seed oils, and accounts for about 80% of the fat composition of vegetable oils. Omega-6 fats must be balanced with omega-3 fats in order to not be harmful, but most Americans don’t eat that way.

Most of the omega-6 people eat, including seed oils, has been damaged and oxidized through processing. Once oxidized, it generates oxidized linoleic acid metabolites, which are mutagenic, carcinogenic, cytotoxic and atherogenic. (R)

How Linoleic Acid Triggers Heart Disease

Goodrich also explains how high LA levels cause heart disease. One of the first things that happens in atherosclerosis is your macrophages, another type of leukocyte, turns into a foam cell, essentially a macrophage stuffed with fat and cholesterol. Atherosclerotic plaque is basically dead macrophages and other types of cells loaded with cholesterol and fat. This is why heart disease is blamed on dietary cholesterol and fat.

However, researchers have found that in order for foam cells to form, the LDL must be modified through oxidation, and seed oils do just this. Seed oils cause the LDL to oxidize, thereby forming foam cells. LDL in and of itself does not initiate atherosclerosis. LDL's susceptibility to this oxidative process is controlled by the LA content of your diet.

Understanding Olive Oil

As mentioned, olive oil also contains LA, but it also has other healthy fats. This makes olive oil a bit tricky. The main fat in olive oil is oleic acid, which is one of your body's favorite fats. Your body actually makes it, which is why it's not considered an essential fat. Oleic acid is much more resistant to oxidation than LA, which is why olive oil is a pretty decent cooking oil.

According to Goodrich, oleic acid is protective against both cardiolipin oxidation and LDL oxidation. Interestingly, oleic acid can also replace LA in LDL. Other fats, such as palmitic acid, cannot do that. The problem with olive oil is that it also has a fair amount of LA.

"The percentages that I've seen quoted in literature range from 2%, which is awesome, to 22%, which is not good," Goodrich says. The other problem is the olive oil market is hugely corrupt and fraught with fraud. Many olive oils are cut with cheaper seed oils, which raises the LA content.

So, in summary, if you're using olive oil, I strongly recommend keeping close track of your total LA intake. Anything over 10 grams a day is likely to be problematic (although the exact cutoff is still unknown, so this is merely an educated guess).

If you really want to be on the safe side, consider cutting LA down to 2 or 3 grams per day, to match what our ancestors used to get before all of these chronic health conditions became widespread. If olive oil puts you over the limit, consider cooking with tallow or lard instead. Beef tallow is 46% oleic acid and lard is 36% oleic acid.

Foods High in Linoleic Acid

As Goodrich suggests, if you want to protect your health, you'd be wise to avoid all concentrated sources of LA. 

Top sources include chips fried in vegetable oil, commercial salad dressings, virtually all processed foods and any fried fast food, such as french fries.

According to the National Cancer Institute, the top sources of dietary linoleic acid in America include chicken and chicken dishes, grain-based desserts, salad dressing, potato and corn chips, pizza, bread, french fries and pasta dishes. Mayonnaise, eggs, popcorn and processed meats are also significant sources.   

The Importance of Carnosine

Beef, even conventional grain-finished beef, has low LA. Grass fed beef has higher DHA and CLA, which makes it a healthier option. Beef is also the primary source of carnosine, which has been shown to be anti-atherogenic.

Carnosine is also a mitochondrial stimulant, a sacrificial scavenger of advanced lipooxidation end products (ALEs), which is very similar to advanced glycation end products (AGEs). AGEs is another name for HNE and all the other reactive oxygen species generated from oxidizing LA.

Carnosine is the most effective scavenger for HNE. Carbonylation of proteins is basically the process through which proteins in your body get damaged and become ineffective. HNE damages 24% of the proteins in your cells, so carnosine can go a long way toward warding off this cellular damage. 

Take Control of Your Health by Lowering Your Linoleic Acid Intake

As you can see, the evidence strongly suggests excessive LA is driving all the killer diseases today. The solution is simple though. Just lower your LA intake. There's an easy way to do this. You don't have to send all your food out for analysis. Simply use an online nutritional calculator such as Chronometer to calculate your daily intake.

Chronometer will tell you how much omega-6 you're getting from your food down to the 10th of a gram, and you can assume 90% of that is LA. Again, anything over 10 grams is likely to cause problems. Since there's no downside to limiting your LA, you'll want to keep it as low as possible, which you do by avoiding high-LA foods.

Keep in mind you'll never be able to get to zero, and you wouldn't want to do that either. 




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