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Chronic Inflammation: The Slow Burn of Disease

 

Chronic Inflammation: The Slow Burn of Disease

By Nicole Crane. B.S., NTP

Ouch! You stub your toe on your bedpost for the hundredth time. Almost instantly, the redness, pain, swelling and heat wash over your toe. These four symptoms are the classic and predictable signs of acute inflammation, and they serve a very important purpose. When you stub your toe, cut your finger, or overwork yourself at the gym, the body responds with acute inflammation. This type of inflammation is a healthy, normal part of the healing process. We have all known acute inflammation at one time or another.  Acute inflammation is how the body heals itself, and it is essential to maintain your health.

There are 4 predictable responses the body has when we develop acute inflammation: redness, heat, swelling and pain. Sometimes if a muscle or joint is injured, a fifth sign – impairment of function of the injured body part – may also occur. All these signs are normal and healthy.  Acute inflammation allows the body to bring more blood to the injured site, which delivers nutrients, white blood cells and other aspects of the immune system in order to allow the body to remove damaged cells and begin the healing process. Acute inflammation is a short term response to an injury, and the body is able to resolve the inflammation and turn it off on its own.  Redness and heat result from the increased blood flow to the site of injury. Swelling results from the accumulation of fluid at the injury site, which is a consequence of the increased blood flow. Finally, swelling can compress nerve endings near the injury, causing the characteristic pain associated with inflammation. Feeling pain is very important to make you aware of the tissue damage – if you are not feeling pain, you cannot tell if you are injured or not. Additionally, inflammation in a joint usually results in a fifth sign (impairment of function), which forces you to limit movement and rest the injured joint to aid in healing. A well-controlled acute inflammatory response has several protective roles: It prevents the spread of infectious agents and damage to nearby tissues, it helps to remove damaged tissue and pathogens, and it assists the body’s repair processes. All these roles are helpful for the body to get rid of cells that no longer function and replace them with healthy, normal cells so the body can continue to function normally. Acute inflammation plays little role in the process of chronic disease – however, what truly is at the root of nearly all disease processes is another type of inflammation, known as chronic inflammation.  The body cannot maintain optimal health with inflammation that lasts for weeks, months or years. 

This second type of inflammation, chronic inflammation, has a significant negative impact on our wellness, vitality and long-term health. Chronic inflammation affects our immune system, tissue function, biochemical reactions, and much more. We develop inflammation because of our food choices, medications, and lifestyle factors such as stress and alcohol use.  Chronic inflammation is at the root of most disease processes in the body. The CDC (Center for Disease Control) stated in 2011 that 7 of the top 10 causes of mortality are directly attributed to inflammation1, which is the physical culprit when you have any of the “itis” diseases. For example, when you have an inflamed tendon, it is called tendonitis. Inflammation is not just pain – it can have serious health consequences.  We cannot have a healthy heart and vascular system2, a healthy liver, or a functioning digestive system when active inflammation is present. Our hormones and our metabolism do not work optimally when we are inflamed, and this can lead to weight gain and poor blood sugar control3.  Even mood and cognitive disorders become significantly worse when the body is inflamed.

One of the main steps that an individual must take is to restore wellness is to help turn off the “slow burn” of chronic inflammation in the body. Chronic inflammation is different from acute inflammation in several significant ways. First off, chronic inflammation lasts months or years instead of days or weeks. Second, it continuously triggers and re-triggers the involvement of the immune system. This begins the cycle of increased inflammation, further damage, and more immune involvement, which causes the body to have trouble trouble turning off the different proteins and other types of cells that trigger the “on and off” switch of inflammation. Inflammation gets stuck in “on mode,” and this begins the disease process in the body. Next time your doctor does lab work, request a test called CRP (C-reactive protein), which measures inflammation in the body. There are several natural therapies for inflammation, such as Omega-3 fatty acids and herbs like turmeric and boswellia that can be very effective inflammation modulators. 

Let’s briefly go over a few of the immune cells at work when it comes to inflammation in the body. The immune system makes several types of signaling proteins called cytokines. These signaling proteins operate very much like sound – they send signals and directions to the various immune cells, so the body can ensure that all our cells are normal, healthy and functioning properly. Cytokines are released by multiple types of immune cells in response to cellular damage, stress, or infection. Cytokines are long-distance messengers, meaning they are produced by cells at the site of inflammation and then released into the blood, carrying information about the inflammatory response throughout the body. They play a very important role in the initiation of inflammation, as well as in the body’s healing process. Where there is a beginning, there must be an end, and this is key to a normal inflammatory process. Cytokines are widespread, and they trigger the “on-switch” of inflammation. Some of the more important cytokines are: Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), tumor necrosis factor alpha (TNF-a) and interleukins. COX-2, which is probably the most well-known cytokine, is the enzyme responsible for creating pro-inflammatory prostaglandins. COX-2 is also the target of NSAIDs, or Non-Steroidal Anti-Inflammatory Drugs (ibuprofen, aspirin) and COX-2 inhibitors (Celebrex®). Another inflammation regulator used by the immune system is called TNF-α. TNF-α is an intercellular signaling protein (cytokine) which can be released by multiple types of immune cells in response to cellular damage, stress, or infection. Originally identified as an anti-tumor compound produced by macrophages (immune cells that “eat” old or bad cells), TNF-α is required for proper immune communication and function. TNF-α may act either alone or with other inflammatory mediators, slowing down the growth of many pathogens. When TNF-α is overproduced, chronic inflammation can occur.  Another type of cell called Nuclear Factor Kappa-B (NF-kB) is also important in the initiation of the inflammatory response. When cells are exposed to damage signals (such as TNF-α or oxidative stress), they activate NF-kB, which turns on the expression of over 400 genes involved in the inflammatory response. Clearly, the process is quite complicated. There are many different types of immune cells involved, and this is just when inflammation needs to be turned on. When the tissue has healed, the inflammation must be turned off, or we get stuck in a vicious cycle of inflammation, damage, and further pro-inflammatory cytokine activity. There are another group of cytokines, which are the signaling proteins of the immune system, whose job it is to resolve inflammation. These are called interleukins. Many interleukins turn off inflammation, but some turn it on and off, which is essential for balance. Balance is key to healthy immune function and normal inflammation pathways. It is very important to allow the body to self-regulate instead of blocking the COX-2 enzyme altogether – this is so important for long term health.4   

There is another type of cell that is just as important as the long-distance, widespread cytokines. They are called eicosanoids, and they are meant to act locally within the same organ, in neighboring cells, or sometimes even strictly in different parts of the same cell in order to elicit immune defenses. There are several families of eicosanoids (including prostaglandins and leukotrienes) that are created by most types of cells in all of our major organs. They play an important roles in inflammation (and anti-inflammation), and also have a variety of functions in cell growth, organ function, digestion, and the constriction and dilation of blood vessels. Eicosanoids are made by different fatty acids, which is why the diet is a critical factor when it comes to deciding whether you have chronic inflammation, or whether your body can resolve inflammation normally and maintain health. 

We have a class of enzymes called COX cyclooxygenase, and another called LOX lipoxygenase that are the main regulators and controllers of local inflammation. Generally, COX enzyme regulators put us on the right path when it comes to turning off inflammation, fever and pain, because they help to reduce a type of immune cell called prostaglandins that have a tendency to promote pain and inflammatory response. LOX enzymes convert fatty acids into leukotrienes, which are important local mediators of inflammation. Several potent inflammatory leukotrienes are produced by 5-LOX. Lipoxygenase enzymes, and the pro-inflammatory factors they produce, play a fundamental role in this process by aiding in the recruitment of white blood cells to the site of inflammation. They also stimulate local cells to produce cytokines, which amplifies the inflammatory response. While COX and LOX enzymes are most often associated with pro-inflammatory processes, it is important to remember that both enzymes also produce factors that inhibit or resolve inflammation and promote tissue repair. Specifically, enzymes that regulate and suppress the action of COX and LOX can help turn inflammation off, and these are quite valuable. The proper transition from the pro- to anti-inflammatory activities of the COX and LOX enzymes is important for the progression of a healthy inflammatory response.5 A certain level of inflammation is essential, or the body would not be able to heal properly and remove damaged cells and infection. This is why NSAID drugs like aspirin and COX-2 inhibitory medications may do more harm than good for the body from a holistic perspective. They do not allow the body to have a normal inflammatory response. Instead those pathways are shut down altogether. The body does not heal properly, and it may become stuck in a state where the tissue is damaged, but the immune system can’t do anything about it. This causes a situation where, unless you take that medication, you will experience pain. This is not considered a healthy method of long-term pain management. What’s more, these drugs can damage the cardiovascular system, liver, kidneys, GI tract, and over months and years, create more inflammation than the original injury.6 “NSAIDs produce an increase in intestinal permeability which depends on dose and frequency,” states Dr. Leo Galland, a Harvard-educated integrative physician. “This creates an increased level of antibodies compared to bacteria in the gut and leads to inflammation that causes a variety of health problems. About 70 to 80 percent of people who take prescription-strength NSAIDs for two weeks will have leaky gut syndrome, based on studies in England.” 7Furthermore, out of about 30 million NSAID users, the side effects of long-term NSAID use caused nearly 103,000 hospitalizations and 16,500 deaths.8 The body’s natural healing process is essential, and if you make nutrition and supplements your weapon, your body can win the fight every time.

A major problem is that these different inflammation regulation enzymes are made from the foods we eat. The vast majority of people in the US are eating a diet that is quite rich in the building blocks of what turns inflammation on, but consume very few foods that build up the inflammation resolvers. We get stuck in that vicious cycle of inflammation, pain and disease because we do not eat nearly enough of the foods that build what the body needs to turn our inflammatory responses off. Inflammation perpetuates damage, and we need more inflammation to heal the new damage – very quickly, acute inflammation can become chronic. Once the flame has been lit, poor food choices, stress, and poor sleep patterns only fuel the fire. While we cannot always control stress or sleep quality, food choices and proper supplements for additional support are entirely in your hands. The type of fat, the amount of sugar, and the form of carbohydrates you eat are some of the main determining factors in whether you will suffer chronic inflammation or maintain overall wellness. The good news, though, is that nature has provided us with several powerful inflammation regulators, like Omega-3 fatty acids found in fish and krill oil, plus herbs like turmeric and boswellia. These work by producing the immune cells that resolve inflammation, so you can finally end the damaging cycle of chronic inflammation. 

There are two families of fatty acids (EFAs) which are critical for many different aspects of our health. Therefore, they have been termed “essential fatty acids”, but this term is somewhat misleading. The term “essential” in biochemistry only means that the body cannot make them; therefore, it is essential that we consume them through the diet. These essential fats are the Omega-3 family and the Omega-6 family. There are many fatty acids that are members of these EFAs, but some are much more important than others, especially when it comes to whether inflammation is kept in “on” mode or has the ability to naturally turn it off.  Generally speaking, Omega-3 fatty acids, especially the ones we find in fish and krill oil, which are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), help create the eicosanoids that turn off localized inflammation. EPA and DHA are so important that nearly all other Omega-3 fats, like ALA found in flax and chia seeds, will be enzymatically converted into EPA and DHA. Most of us do not get nearly enough Omega-3 in our diet, and this is the first problem with chronic inflammation. EPA and DHA are essential to the production of prostaglandins that resolve inflammation. The second problem is Omega-6 fats, which produce the enzymes that turn and keep inflammation active and in “on” mode, are naturally widespread in many foods.  As mentioned, inflammation is a delicate dance, and some inflammation is vital to acute inflammation and to the healing process.  A healthy diet has an Omega 6:3 ratio that is 4:1 or less. There are many healthy foods that contain more Omega-6 fat than Omega-3 fat, and there is nothing wrong with this. The bigger problem is that all processed foods, and our food supply in general, is completely oversaturated with processed Omega-6 fats that have been isolated from foods. These are mostly refined foods containing corn oil, canola oil, soybean oil and other industrially-produced vegetable fats. A soybean or an ear of corn is not naturally a high-fat food, so when we isolate these fats out and add them to foods, we drastically increase the ratio of Omega 6:3 in our diets. Unfortunately, it is a huge challenge to find a packaged food in the average grocery store that does not contain these pro-inflammatory Omega-6 fats. A diet rich in fruits and vegetables, grass-fed beef, wild caught salmon, tuna, and other oily fish like sardines and anchovies, is a far cry from the “Standard American Diet”. As its acronym suggest, this diet is quite sad! While other cultures cook with herbs and spices that help regulate inflammation, the only seasoning universal in American cooking is processed salt – very sad indeed.   

The good news is that you can change your diet today!  If you don’t read food labels already, start looking for these inflammation producers in the food you buy. You can expect to find these processed Omega-6 oils in margarine, mayonnaise, sauces, most baked goods, and packaged foods in general. There is one place that Omega-6 fats hide that you might not expect, and that’s in grain and corn-fed beef. These days, that’s nearly all the beef produced in the US. Cows are meant to eat grass, so when they eat a diet that is unhealthy for their needs (just like humans), they become inflamed. The fats that become stored in the cows’ muscles – and in the meat you eat – is disproportionally high in Omega-6 fats. The ratio of Omega-6 to Omega-3 in corn fed beef can be as high as 27:1. When cows are fed grass, the Omega 6 to 3 ratio becomes a very healthy 3 or 4:1, which is the same fatty acid profile as salmon. We become inflamed when the Omega 6 to 3 ratio in our overall diet exceeds 4:1, so if you are a big meat eater, choose grass-fed beef. It could make a world of difference in your “itises” and inflammation! The other food to watch out for these oils in salad dressing, as 99% of bottled dressings are made with soybean or canola oil.  Your best bet is to make your own salad dressing. If you want to gain the full benefits of those veggies in your salad, make your own dressing with olive oil or even flax oil, which is a good source of the Omega-3 fat called ALA (Alpha-Linolenic Acid). 

ALA is the main fatty acid found in nuts and seeds. ALA is healthy, but EPA and DHA from fish sources are the healthiest. EPA and DHA make the eicosanoids that help turn off inflammation. They play a vital role in helping the immune system resolve the inflammatory response. Without these fats, inflammation never gets turned off.  Mother Nature, in her infinite wisdom, gave us these perfect fats that help the body regulate inflammation as we need it. If we need to heal, Omega-3 fats can help us make the immune cells that turn inflammation on.  Then when we are all healed up, these fats turn the inflammation off, and everything goes back to normal. It’s a beautiful dance, it is balance and synergy. Not all Omega-6 fats are bad, either. There are many types of fatty acids in the Omega-6 family, such as borage oil, evening primrose oil, and hemp oil, all of which contain high levels of a fatty acid called GLA, or gamma linoleic acid. GLA plays a major role in building the immune cells that turn inflammation off, and those are great to include in the diet or take as supplements. 

These two fatty acids make more of the inflammation-resolving proteins than any other fatty acid that the body can use. That’s why fish and krill oil are so good for the heart, brain, joints, GI tract, and every single other part of the body. EPA and DHA are essential to the production of prostaglandins and eicosanoids that turn off inflammation, therefore turning off disease. They keep every cell in the body healthy and functioning normally. They keep the body in harmony and balance. The benefits of EPA include supporting cardiovascular wellness, mainly by regulating and turning off inflammation that initiates and perpetuates vascular damage. EPA also supports normal heart rhythm, healthy blood clotting, and normal triglyceride levels. EPA supports healthy brain function, mood and mental health as well, largely due to positive inflammation modulation which allows for normal neurotransmitter production.  EPA also supports digestive health through inflammation regulation, allowing a damaged GI tract to properly heal and interact with the immune system in a positive way.  EPA has positive effects on immune function, which requires a balanced inflammatory response in order to function optimally.  EPA also suppresses the production of nuclear factor-KB, a substance in cells that is responsible for regulating the expression of genes involved in inflammation. A wide variety of research has shown EPA has positive and protective effects on nearly every body system. EPA tends to improve nearly all conditions that are inflammatory in origin, quelling the inflammatory fires that feed disease. 9

As impressive as the health benefits of EPA are, DHA is the ultimate fatty acid that supports optimal health. DHA is not a substrate for prostaglandin production, and it tends to inhibit the enzymes that allow for prostaglandin synthesis if EPA and DHA are out if balance. However, DHA is the precursor of the docosanoids. Docasanoids are the precursors for resolvins and protectins, which are comparable to the eicosanoids and have potent inflammation modulation and immuno-regulatory actions. DHA is believed to have specific effects on gene transcription that regulate a number of proteins involved in making different fatty acids. It has been shown to have beneficial effects on inflammatory disorders of the intestinal tract, likely due to regulation of specific signaling proteins in cell membranes, and not prostaglandin activity. DHA has many of the same health benefits of EPA, but as EPA tends to improve inflammatory responses, DHA tends to improve nerve and neurological health as well as cell-to-cell communication. DHA is a major component of phospholipids, especially those in the cell membranes of brain synapses. DHA is also found in high concentration in the retina, where it is a major structural component of the photoreceptor outer segment membranes. DHA also binds strongly to specific sites on rhodopsin, the primary light receptor in the eye, supporting vision in a significant way. Although adequate amounts of DHA are especially important during pregnancy and infancy, this fatty acid plays a vital role in supporting brain function throughout life. Up to 45% of the fatty acids in synaptic membranes are composed of EPA and DHA. Adequate DHA intake is necessary for optimal nerve communication. DHA has also been shown to support healthy and normal mental health. Like EPA, DHA has impressive cardio-protective effects. It also reduces blood clotting, controls inflammation, supports healthy triglyceride levels, and promotes cell membrane health in the heart, thus supporting a normal heart rhythm. DHA can even support healthy lung function by decreasing the formation of pro-inflammatory leukotrienes made from the Omega-6 fat arachadonic acid that acts as a blood vessel constrictor, benefiting those with asthma.10  EPA and DHA have wonderful widespread benefits for the whole body.

There are some powerful, natural herbs that can make a significant difference in pain and the body’s inflammatory response. When it comes to herbal medicine and inflammation, the spice turmeric is the most powerful, most effective remedy for cooling inflammation. A close second is the Ayurveda herb Boswellia, otherwise known as frankincense. Seek a supplement that includes these herbs to help the body produce less of the proteins that have a pro-inflammatory action. Again, in the beautiful wisdom of Mother Nature, inflammation is not simply shut off like a light, which is the way NSAID drugs work. In this situation, the body is not allowed to self-regulate. Instead, these herbs act like a dimmer switch.  They let the injury heal or the immune system get rid of the infection, but when that is completed they make sure inflammation is turned off. Otherwise, the body becomes stuck in a vicious cycle of inflammation that will not subside, leading to damage that perpetuates the inflammation. Turmeric/Curcumin supports immunity, and because of the essential role it plays in a healthy inflammatory response, it’s great for the brain, the heart, the GI tract, all of the joints and tendons, lungs, and muscles. 11, 12 If you have pain, inflammation, and disease in any part of your body, and if you have any form of “itis”, fish oil or krill oil would be a great addition to your nutrition protocol.

There is one more aspect of diet that is important to address. Sugar is all its many forms creates a huge amount of pro-inflammatory molecules, which turn on inflammation and pain. The best thing you can do to prevent inflammation and disease is to give up sugar and all refined carbs, but that’s much easier said than done. Try to limit soda, candy, bread, pasta, rice, cookies, cake, and all the other foods sugar hides in as much as you can – you will feel much better overall. Sugar, especially fructose and high-fructose corn syrup, creates something called advanced glycation end products, or AGES, that are aptly named because they age our body at a very fast rate. AGEs are sugars that attach to the proteins in our body, causing damage and inflammation to structural proteins as in the eyes, skin, joints and tendons, and every other part of your body. This damage causes inflammation, and if the body does not have the right nutrition to turn it off, we tend to age more quickly by developing wrinkles, older-looking skin, stiff joints, and pain with movement. AGEs also damage proteins that make up the hormones and enzymes that drive all our biochemical processes, and this may have a variety of consequences including mood and brain issues, hormonal imbalances, low energy levels, sensitivity to stress and poor sleep patterns. Depending on what becomes damaged, for example nerves or hormone cells, diseases can develop and worsen over time.13 If you have chronic inflammation, do your best to cut sugar. I know it can be incredibly hard, but it is well worth giving up sugar for good. The modern American diet drives all the pathways that turn inflammation on, but we have very few sources that help to turn inflammation off. Inflammation is biochemical, and you can use food and supplements to maintain a healthy, balanced, and normal inflammatory response.   

Inflammation is an issue that plagues many people, and years of damage and pain cannot be healed overnight. But by making some positive changes in your diet, eating and drinking less sugar, choosing high-quality meats, and cutting down on soda, sweets, and processed food, you can shift the balance and help the body create less of the proteins that turn inflammation on. By introducing a key supplements like Krill Oil, you can help your body make the proteins that turn inflammation off and bring the body back into balance and optimal health. It is possible to live without pain, inflammation and disease! Having optimal health is your right, and something you deserve. Change your diet, add some supplements, and cool down the slow burn of inflammation. Managing inflammation is the first and most important step in supporting your overall health for the entire length of your life.

Challem, Jack, The Inflammation Syndrome, Hoboken, NJ; John Wiley and Sons Publishing, 2010

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