The Role of Polyunsaturated Fats in Inflammation

It may surprise you to learn that your ability to regulate inflammation depends largely on a balanced dietary intake of polyunsaturated fats (PUFAs), which are found in many foods and supplements. In essence, your body makes both pro- and anti-inflammatory compounds using PUFAs as their biochemical building blocks.

When it comes to inflammation, two families of PUFA’s are of major concern—the omega-3s and the omega-6s. As a general rule, the omega-6 family of PUFAs promote inflammation. In contrast, the omega-3 family of PUFAs reduce inflammation. There are, however, important exceptions to the rule—some omega-6 fats actually have impressive anti-inflammatory properties.

Many people do not consume optimal ratios of the omega-6 and omega-3 fats, which are also known as fatty acids. In ancient times, people consumed roughly equal amounts of omega-6 and omega-3 fats—a 1:1 ratio. Because of widespread food processing, the dietary ratio of omega-6 to omega-3 fats now ranges from 15:1 to 30:1.¹ This change alone primes the body toward more inflammation.

It takes a little time to figure out how to use dietary PUFAs and supplements to your advantage. The reason is that PUFAs are one of the more complicated aspects of nutrition. Why is this? One reason is that the body converts dietary PUFAs to more potent pro- and anti-inflammatory compounds through an intricate series of biochemical steps. Another is that different compounds have similar and confusing names.

To simplify the steps, it helps to visualize the steps as a series of steppingstones, basically going from point A to point D. I’ll explain some of the key steps, as well as what can go wrong.

The Key Omega-6 Fats

The “parent” molecule of omega-6 fats is linoleic acid. It’s found in seeds and nuts, but the major dietary sources are now common cooking oils, including corn, peanut, safflower, soybean oils. Linoleic acid doesn’t have much biological activity on its own, though all other omega-6s are made from it.

What happens? Certain enzymes, including delta-6-desaturase, convert linoleic acid to more useful compounds. This process begins with linoleic acid being changed to gamma-linolenic acid (GLA). Next, GLA rapidly converts to dihomogamma-linolenic acid, or DGLA. (Blame the convoluted names on biochemists!)

Then what happens? Some DGLA gets converted to anti-inflammatory compounds, including prostaglandin E₁—that’s good. However, some DGLA gets converted to arachidonic acid (AA), and that’s bad. AA is the hub of the body’s inflammation- promoting network, and it turns into very powerful inflammation-causing compounds, including prostaglandin E₂.

The Key Omega-3 Fats

The parent molecule of omega-3 fats is alpha-linolenic acid. It’s naturally found in leafy green vegetables (e.g., kale and dark lettuces), flaxseed, and coldwater fish (e.g., salmon and herring). Alpha-linolenic acid doesn’t do much on its own, but all other omega-3s are made from it.

What happens? Various enzymes convert alpha-linolenic acid to eicosapentaenoic acid (EPA) and, subsequently, to docosahexaenoic acid (DHA). EPA is the precursor to prostaglandin E₃, which is good. Prostglandin E₃ has an anti-inflammatory effect because it slows production of prostaglandin E₂.

Why is fish oil so good – and flaxseed oil not so good? Fish oils, whether found in coldwater fish or capules, contain “preformed” EPA and DHA. (The fish convert alpha-linolenic acid to EPA and DHA.) The EPA and DHA in fish or fish oil capsules leapfrogs many of the steps involved in converting alpha-linolenic acid to more biologically active compounds. That’s why fish oils have such significant anti-inflammatory benefits.

Is flaxseed oil a substitute for fish oils? No. Flaxseed oil is not equivalent to fish oils, either nutritionally or in terms of anti-inflammatory benefits. Although flaxseed is frequently touted as a source of omega-3 fats, it provides alpha-linolenic acid, which the body must convert to EPA and DHA. This conversion is far easier said than done. Because of either nutritional deficiencies or too many omega-6 fats thwarting the conversion, many people do not efficiently—nor sufficiently—convert alpha-linolenic acid in flaxseed oil to EPA and DHA.² Bottom line? Flaxseed oil is a poor alternative to fish oil as a source of the all-important omega-3s EPA and DHA.

Vegetarians who want to avoid fish products can supplement with EPA and DHA derived from algae.

What Goes Wrong?

A variety of factors disrupt the body’s normal processing of fats, leading to more inflammation. Even when an inflammatory response is necessary, such as after an injury or when fighting an infection, the body often has difficulty turning off the inflammatory reaction. The result is chronic inflammation.

Here are some of the reasons why things go wrong:

First, nature favors the pro-inflammatory properties omega-6 fats. That’s probably because infection has always been the leading cause of death, and people have needed a robust infection-fighting immune system, which depends largely on omega-6 fats.

Second, the massive amounts of omega-6 fats in the modern diet dwarfs the tiny amounts of omega-3 fats, leading to a pro-inflammatory imbalance.

Third, the formation of an important fat-processing enzyme, delta-6-desaturase, depends on adequate levels of vitamin B6, magnesium and zinc. Deficiencies of these nutrients are common, affecting more than one-third of Americans, according to data from the US Department of Agriculture. Low levels of these nutrients create a biochemical bottleneck that blocks delta-6-desaturase production and, subsequently, production of anti-inflammatory compounds.

Fourth, the activity of delta-6-desaturase is also blocked by trans fats, found in hydrogenated oils. As a result, trans fats inhibit the conversion of linoleic acid to anti-inflammatory GLA. In effect, trans fats promote inflammation.

Fifth, some foods contain large amounts of pro-inflammatory arachidonic acid. These foods include grain-fed (e.g., corn-fed) beef and pork, as opposed to grass-fed meats. Likewise, farmed fish contain large amounts of arachidonic acid, as opposed to wild fish.

Sixth, high insulin levels increase the activity of an enzyme, delta-5-desaturase, which increases the body’s production of pro-inflammatory arachidonic acid. This is significant because upwards of 100 million Americans may have elevated insulin levels, a sign of prediabetes.

Some Helpful Definitions

Confused about the difference between an omega-6 and omega-3 or the many types of prostaglandins? These definitions should help.

• Alpha-linolenic acid. The parent molecule of the omega-3 family of fats. It’s found in coldwater fish, leafy green vegetables, and flaxseed.
• Arachidonic acid. A key arbiter of inflammation. This member of the omega-6 family is the building block of many inflammation-promoting substances. It’s found in meat from grain (e.g., corn) fed animals, as well as farm-raised fish
• Docosahexaenoic acid (DHA). An anti-inflammatory member of the omega-3 family. It’s found in fish oil and in vegetarian algae-based supplements.
• Eicosapentaenoic acid (EPA). A potent anti-inflammatory member of the omega-3 family. It counters arachidonic acid. EPA is found in fish oils.
• Linoleic acid. The parent molecule of the omega-6 family of fats. It’s found in many common cooking oils.
• Gamma-linolenic acid (GLA). An anti-inflammatory member of the omega-6 family. It’s found in borage, evening primrose, and black currant seed oils.
• Omega-3. An essential family of dietary polyunsaturated fats. Omega-3 fats tend to be anti-inflammatory.
• Omega-6. An essential family of dietary polyunsaturated fats. The omega-6 fats tend to be pro-inflammatory, with the notable exception of gamma-linolenic acid.
• Prostaglandins. Hormone-like substances, made from dietary fats, that regulate inflammation in the body.
• Prostaglandin E1. A byproduct of gamma-linolenic acid with anti-inflammatory properties.
• Prostaglandin E2. A byproduct of arachidonic acid with strong pro-inflammatory properties.
• Prostaglandin E3. A byproduct of EPA that reduces the activity of prostaglandin E2. As a result, prostaglandin E3 is anti-inflammatory.

The Best Anti-Inflammatory Fats

Supplements of omega-3 fish oils and GLA have the advantage of bypassing many of biochemical bottlenecks that interfere with the body’s handling of PUFAs. Here’s an overview of research on them.

Omega-3 Fish Oils

Much of the anti-inflammatory effect of omega-3 fish oils derives from its EPA, which competes against arachidonic acid.³ Many studies have found that the omega-3 fish oils reduce the risk of coronary heart disease. They are also mild blood thinners, slow the heart rate, improve heart rhythm, and improve blood-vessel flexibility.^4 5 Some evidence suggests that omega-3 fats may inhibit the growth of cancers.^{6 7}

People who consume a lot of omega-3 fish oils have a lower risk of developing Alzheimer’s disease. In a Swedish study, researchers gave an omega-3 fish oil supplement to 174 men and women with Alzheimer’s disease. People with mild (but not severe) cognitive impairment improved during six months of supplementation.⁸

The omega-3 fats are also needed for normal brain function. Considerable research has found that omega-3 fish oils can benefit people with depression, postpartum depression, and bipolar disorder.^{9 10 11} Other studies have found that the omega-3s can reduce impulsive behavior, hostility, and physical aggressiveness.^{12 13 14} DHA in particular may also improve memory and help cognitive function.^{15 16}

In addition, dry eye syndrome may be helped with increased consumption of omega-3 fats. A Harvard University study of more than 32,000 women found that women who consumed a lot of omega-3 fats had a relatively low risk of developing dry eyes. In contrast, women who consumed a lot of omega-6 fats but little omega-3 fats were more likely to suffer from dry eyes.¹⁷

For most people, the beneficial amount of omega-3 fish oils ranges from 1,000 to 3,000 mg daily.

Gamma-Linolenic Acid

Several studies have found that GLA supplements can significantly lessen symptoms of rheumatoid arthritis.^{18 19 20} Because GLA inhibits several promoters of inflammation (including tumor necrosis factor, interleukin-1 beta) it may have benefits in a range of inflammatory disorders.^{21 22 23} Studies have also found that GLA is helpful in resolving atopic dermatitis (eczema) and psoriasis.^{24 25 26}

The beneficial amount appears to be at least 275 mg taken twice daily.

Combining GLA with vitamin D and omega-3 fish oils may enhance its benefits.

GLA may also help people maintain a healthy weight. In a study at the University of California, Davis, people who had recently lost weight and took GLA supplements were less likely to regain weight, compared with people taking placebos.²⁷ GLA supplements are obtained from borage seed, black currant seed, and evening primrose seed oils. Ounce for ounce, borage seed oil contains the most GLA. However, it’s important to read supplement labels carefully—the key is the specific amount of GLA, not the borage, black currant, or evening primrose oils.

The beneficial amount of GLA ranges from about 550 mg to 2.4 grams (2,400 mg) daily.

Other Considerations

Combining omega-3 fats with gamma-linolenic acid may yield optimal anti-inflammatory benefits. For more than 10 years now, the Danish Olympic team has used a combination of these two supplements to treat inflammatory over-use injuries in athletes. The dosages are approximately 700 mg each of omega-3 fish oils and gamma-linolenic acid.²⁸

It’s always important to emphasize fresh, healthy foods as the foundation of an anti-inflammatory diet. These foods include fish (e.g., salmon and herring), free-range chicken and turkey, and grass-fed beef. Grass is high in alpha-linolenic acid, which ruminants efficiently convert to EPA and DHA. In addition, eat plenty of high-fiber, nonstarchy vegetables and fruits, including salads, broccoli, cauliflower, raspberries, and blueberries. Limit your intake of grains, which are high in omega-6 fats.

Extra-virgin olive oil is rich in oleic acid, an omega-9 monounsaturated fat, which is also anti-inflammatory. Saturated fats don’t play a big role in inflammation, though they are often found with omega-6 fats and chemically modified fats in processed foods.

In sum, contemporary processed foods high in omega-6 fats (i.e., corn, peanut, safflower, and soybean oils), as well as chemically modified fats, tend to promote inflammation. Conversely, fresh foods— particularly coldwater fish and leafy green vegetables—enhance the body’s innate anti-inflammatory processes. And, supplements have the advantage of circumventing some of the biochemical bottlenecks that interfere with normal PUFA metabolism.

Antioxidants Can Also Protect Against Inflammation

• Harmful molecules called free radicals trigger the release of cell-communication molecules called cytokines. Some of these cytokines signal cells to convert arachidonic acid to a variety of inflammation-promoting compounds.
• Antioxidants are well known for their ability to quench free radicals. In the process, they also dampen inflammation.
• One of the most powerful natural anti-inflammatory compounds is curcumin, found in the spice turmeric. It inhibits almost 100 promoters of inflammation, according to a recent article in Biochemical Pharmacology.¹ Pycnogenol^®, a proprietary extract of French maritime pine trees, also has potent anti-inflammatory properties.
• Many other common antioxidants have anti-inflammatory benefits. They include vitamins E and C, as well as citrus bioflavonoids.

References

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