David Baxter PhD
Late Founder
Why Inflammation is a Hot Topic
Berkeley Wellness
September 15, 2014
You know what inflammation looks like: You get a cut or bruise, and the area around it soon turns red, gets warm, and swells up. This is called the acute inflammatory response, and it?s your immune system?s defensive reaction to infection or injury. A complex array of immune cells congregate at the site and release a variety of chemicals to deal with the infectious organisms or debris from the injury and to allow tissue repair to begin; normally the inflammation gradually subsides. This immune response is essential to life.
But there?s another way inflammation works?it can be chronic and cause a low-grade systemic reaction. Because it increases with aging, it has been dubbed ?inflammaging.? Chronic systemic inflammation has been the focus of a great deal of scientific attention during the past two decades (especially the past few years) and is now viewed as a sort of ?unified field? explanation for many, if not most, age-related chronic diseases.
Accordingly, factors (genetic, lifestyle, and environmental) that promote chronic inflammation or disrupt the body?s protective mechanisms against it may increase the risk of premature aging and the disorders that go with it. On the other hand, healthy aging and longevity may be related to reduced levels of inflammation and/or strong protective mechanisms that guard against its adverse effects.
This was suggested by the results of a study in the Canadian Medical Association Journal last year, which included 3,000 British civil servants. It found a strong link between higher levels of chronic inflammation (as measured by blood levels of an inflammatory marker) and a decreased likelihood of ?successful aging,? defined as optimal physical and cognitive health and the absence of chronic diseases. In fact, elevated levels of inflammation appeared to reduce the odds of successful aging by half over the next decade and to markedly increase the odds of cardiovascular disease and death.
Many complex roles
Researchers have found that chronic inflammation is involved, to varying extents, in everything from coronary artery disease, cancer, obesity, and type 2 diabetes to Alzheimer?s, chronic obstructive pulmonary disease (COPD), allergic conditions such as asthma, and autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease.
But how exactly is inflammation involved? Does it cause chronic diseases, result from them, or simply accompany them (perhaps because the factors that contribute to the diseases also increase inflammation)? Inflammation appears to play all these roles. It can be both a cause and an effect of some disorders?setting up a vicious cycle that helps explain their chronic nature.
For example, chronic inflammation plays reciprocal roles with obesity and insulin resistance. It contributes to the development of insulin resistance, which in turn may help promote obesity. Conversely, obesity worsens insulin resistance and increases chronic inflammation, partly because body fat (especially the type surrounding internal organs) releases pro-inflammatory compounds. In effect, inflammation, obesity, and insulin resistance reinforce one another, often resulting in type 2 diabetes. What?s more, many lifestyle factors that promote inflammation, such as being sedentary and having an unhealthy diet, also promote obesity and insulin resistance.
A relatively new theory about chronic inflammation involves the human microflora?the trillions of bacteria and other organisms living in the colon, on the skin, and elsewhere in the body. Changes in the microflora caused by lifestyle and environmental factors (such as diet, antibiotic use, and air pollution) may play a role in the increase in inflammatory diseases in the industrialized world.
Hard to pin down
Chronic inflammation is a varied phenomenon that affects nearly every aspect of human physiology and disease development. Many different kinds of specialized cells and chemicals are involved in producing and regulating these inflammatory processes.
Since it is so complex, there is no way to measure chronic inflammation directly. Instead, researchers measure a variety of inflammatory chemical markers in the blood or tissue, notably interleukin-6, tumor necrosis factor (TNF), C-reactive protein (CRP, see inset), prostaglandins, and leukotrienes. Elevated levels of these factors are good indicators of disease activity for some conditions (such as inflammatory bowel disease). But it?s not clear whether measuring them adequately gauges inflammation and the resulting risks for some other disorders (such as cancer).
C-reactive protein, or CRP, is produced by the liver in response to inflammation. Of all markers for inflammation, it has gotten the most attention because research has shown that elevated blood levels are strongly associated with an increased risk of cardiovascular disease, even in people otherwise at low risk.
The link to heart disease
For many years atherosclerosis was seen as a kind of plumbing problem?that is, merely a matter of plaque building up in the walls of coronary arteries and clogging them. But blood vessels are nothing like pipes?they are active tissue involved in complex processes. In simplest terms, cells lining the vessels absorb cholesterol (and other substances) from the blood, leading to the build-up of plaque. The body perceives this plaque as an injury and sends inflammatory cells into the vessel walls, where they set off a cascade of events that can ultimately cause plaque to rupture and a clot to form over it. If the clot breaks off or otherwise obstructs blood flow to the heart or brain, this can result in a heart attack or stroke.
It now appears that inflammation plays key roles in all stages of the development of cardiovascular disease. Bacterial or viral infection may also trigger the inflammatory process in blood vessels. Meanwhile, coronary risk factors such as obesity, high blood pressure, undesirable cholesterol levels, and smoking cause or worsen arterial inflammation. Having an inflammatory disorder, such as rheumatoid arthritis, diabetes, or inflammatory bowel disease, also increases coronary risk.
Some medications that help prevent heart attacks and strokes, notably statins, do so at least in part by reducing inflammation. The story is more complicated regarding aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). At the low doses used to protect the heart, aspirin has only a small effect on inflammation; its heart benefit comes primarily from its ability to reduce the risk of blood clots. No other NSAIDs are good for the heart. In fact, some NSAIDs, notably celecoxib (Celebrex), increase the risk of heart attacks slightly.
The cancer connection
As early as the mid-19th century, scientists found links between chronic inflammation (or its markers) and cancer. It?s now estimated that more than 20 percent of cancer cases are associated with inflammation.
Inflammation is involved with cancer development on many levels. Notably, it contributes to tumor initiation by inducing oxidative stress, DNA damage, and chromosomal instability. It promotes tumor cell proliferation and resistance to apoptosis (programmed cell death after a certain number of cell divisions, a good thing when it comes to cancer cells). Simply put, increased inflammation makes it easier for normal cells to transform into malignant cells.
The evidence is strongest concerning gastrointestinal cancers, including certain kinds of colon, liver, esophageal, and stomach cancer. It?s theorized that these organs are at high risk because they are exposed directly to pro-inflammatory dietary and environmental factors. Inflammation can also alter colonic microflora in ways that increase cancer risk.
On the positive side again, evidence is accumulating that aspirin, partly because of its anti-inflammatory effect, can reduce the risk of certain types of colon cancer and possibly certain other cancers.
What does all this mean for you?
What can you do to reduce chronic inflammation and the risks it entails? There is no magic food, pill, or treatment. But many of the same steps that help prevent cardiovascular disease may do so in part by helping to tamp down inflammation.
On the horizon
Researchers are developing a number of drugs that target chronic inflammation in hopes of reducing the risk of chronic diseases, especially cardiovascular disease. But inflammation?s complexity makes this a tricky task. Even if a drug lowers levels of certain inflammatory markers, that doesn?t necessarily mean there will be a benefit in terms of disease prevention or treatment. What?s more, since the inflammatory response is essential for survival, it would be risky to tamp it down too much.
Berkeley Wellness
September 15, 2014
You know what inflammation looks like: You get a cut or bruise, and the area around it soon turns red, gets warm, and swells up. This is called the acute inflammatory response, and it?s your immune system?s defensive reaction to infection or injury. A complex array of immune cells congregate at the site and release a variety of chemicals to deal with the infectious organisms or debris from the injury and to allow tissue repair to begin; normally the inflammation gradually subsides. This immune response is essential to life.
But there?s another way inflammation works?it can be chronic and cause a low-grade systemic reaction. Because it increases with aging, it has been dubbed ?inflammaging.? Chronic systemic inflammation has been the focus of a great deal of scientific attention during the past two decades (especially the past few years) and is now viewed as a sort of ?unified field? explanation for many, if not most, age-related chronic diseases.
Accordingly, factors (genetic, lifestyle, and environmental) that promote chronic inflammation or disrupt the body?s protective mechanisms against it may increase the risk of premature aging and the disorders that go with it. On the other hand, healthy aging and longevity may be related to reduced levels of inflammation and/or strong protective mechanisms that guard against its adverse effects.
This was suggested by the results of a study in the Canadian Medical Association Journal last year, which included 3,000 British civil servants. It found a strong link between higher levels of chronic inflammation (as measured by blood levels of an inflammatory marker) and a decreased likelihood of ?successful aging,? defined as optimal physical and cognitive health and the absence of chronic diseases. In fact, elevated levels of inflammation appeared to reduce the odds of successful aging by half over the next decade and to markedly increase the odds of cardiovascular disease and death.
Many complex roles
Researchers have found that chronic inflammation is involved, to varying extents, in everything from coronary artery disease, cancer, obesity, and type 2 diabetes to Alzheimer?s, chronic obstructive pulmonary disease (COPD), allergic conditions such as asthma, and autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease.
But how exactly is inflammation involved? Does it cause chronic diseases, result from them, or simply accompany them (perhaps because the factors that contribute to the diseases also increase inflammation)? Inflammation appears to play all these roles. It can be both a cause and an effect of some disorders?setting up a vicious cycle that helps explain their chronic nature.
For example, chronic inflammation plays reciprocal roles with obesity and insulin resistance. It contributes to the development of insulin resistance, which in turn may help promote obesity. Conversely, obesity worsens insulin resistance and increases chronic inflammation, partly because body fat (especially the type surrounding internal organs) releases pro-inflammatory compounds. In effect, inflammation, obesity, and insulin resistance reinforce one another, often resulting in type 2 diabetes. What?s more, many lifestyle factors that promote inflammation, such as being sedentary and having an unhealthy diet, also promote obesity and insulin resistance.
A relatively new theory about chronic inflammation involves the human microflora?the trillions of bacteria and other organisms living in the colon, on the skin, and elsewhere in the body. Changes in the microflora caused by lifestyle and environmental factors (such as diet, antibiotic use, and air pollution) may play a role in the increase in inflammatory diseases in the industrialized world.
Hard to pin down
Chronic inflammation is a varied phenomenon that affects nearly every aspect of human physiology and disease development. Many different kinds of specialized cells and chemicals are involved in producing and regulating these inflammatory processes.
Since it is so complex, there is no way to measure chronic inflammation directly. Instead, researchers measure a variety of inflammatory chemical markers in the blood or tissue, notably interleukin-6, tumor necrosis factor (TNF), C-reactive protein (CRP, see inset), prostaglandins, and leukotrienes. Elevated levels of these factors are good indicators of disease activity for some conditions (such as inflammatory bowel disease). But it?s not clear whether measuring them adequately gauges inflammation and the resulting risks for some other disorders (such as cancer).
C-reactive protein, or CRP, is produced by the liver in response to inflammation. Of all markers for inflammation, it has gotten the most attention because research has shown that elevated blood levels are strongly associated with an increased risk of cardiovascular disease, even in people otherwise at low risk.
The link to heart disease
For many years atherosclerosis was seen as a kind of plumbing problem?that is, merely a matter of plaque building up in the walls of coronary arteries and clogging them. But blood vessels are nothing like pipes?they are active tissue involved in complex processes. In simplest terms, cells lining the vessels absorb cholesterol (and other substances) from the blood, leading to the build-up of plaque. The body perceives this plaque as an injury and sends inflammatory cells into the vessel walls, where they set off a cascade of events that can ultimately cause plaque to rupture and a clot to form over it. If the clot breaks off or otherwise obstructs blood flow to the heart or brain, this can result in a heart attack or stroke.
It now appears that inflammation plays key roles in all stages of the development of cardiovascular disease. Bacterial or viral infection may also trigger the inflammatory process in blood vessels. Meanwhile, coronary risk factors such as obesity, high blood pressure, undesirable cholesterol levels, and smoking cause or worsen arterial inflammation. Having an inflammatory disorder, such as rheumatoid arthritis, diabetes, or inflammatory bowel disease, also increases coronary risk.
Some medications that help prevent heart attacks and strokes, notably statins, do so at least in part by reducing inflammation. The story is more complicated regarding aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). At the low doses used to protect the heart, aspirin has only a small effect on inflammation; its heart benefit comes primarily from its ability to reduce the risk of blood clots. No other NSAIDs are good for the heart. In fact, some NSAIDs, notably celecoxib (Celebrex), increase the risk of heart attacks slightly.
The cancer connection
As early as the mid-19th century, scientists found links between chronic inflammation (or its markers) and cancer. It?s now estimated that more than 20 percent of cancer cases are associated with inflammation.
Inflammation is involved with cancer development on many levels. Notably, it contributes to tumor initiation by inducing oxidative stress, DNA damage, and chromosomal instability. It promotes tumor cell proliferation and resistance to apoptosis (programmed cell death after a certain number of cell divisions, a good thing when it comes to cancer cells). Simply put, increased inflammation makes it easier for normal cells to transform into malignant cells.
The evidence is strongest concerning gastrointestinal cancers, including certain kinds of colon, liver, esophageal, and stomach cancer. It?s theorized that these organs are at high risk because they are exposed directly to pro-inflammatory dietary and environmental factors. Inflammation can also alter colonic microflora in ways that increase cancer risk.
On the positive side again, evidence is accumulating that aspirin, partly because of its anti-inflammatory effect, can reduce the risk of certain types of colon cancer and possibly certain other cancers.
What does all this mean for you?
What can you do to reduce chronic inflammation and the risks it entails? There is no magic food, pill, or treatment. But many of the same steps that help prevent cardiovascular disease may do so in part by helping to tamp down inflammation.
- Eat a heart-healthy diet. Lab research has shown that many healthful foods, especially fatty fish, fruits, and vegetables (as well as chocolate, wine, and tea) have anti-inflammatory effects. Other studies have shown that the Mediterranean diet tends to reduce inflammation (as measured by CRP). On the other hand, saturated fats, trans fats, sugar, and other refined carbohydrates have pro-inflammatory effects in the body.
- Aerobic exercise, done regularly and moderately, reduces chronic inflammation via a variety of complex mechanisms. In contrast, being sedentary or training very intensely both increase inflammation.
- If you are very overweight, and especially if the extra pounds are in your abdomen, lose weight via a healthy diet and exercise. That will reduce inflammation and the risk of chronic diseases.
- Don?t smoke?it?s a powerful cause of inflammation. Avoid secondhand smoke.
- If you have had a heart attack or are at elevated risk for one, talk to your doctor about low-dose aspirin. If you have no history of cardiovascular disease, however, the risks of aspirin therapy (bleeding in the stomach or brain) may outweigh its small benefit. Similarly, if you are at high risk for colon cancer because of polyps or family history, discuss aspirin therapy with your doctor.
- If you?re prescribed a statin, here?s an added reason to take it: It serves double duty?against cholesterol and inflammation.
- Don?t drink more than moderate amounts of alcohol.
- Get adequate sleep and try to find ways to deal with stress, anxiety, and depression. Social isolation can also increase chronic inflammation, as was seen in a study in the Journal of Health and Social Behavior last year, so increasing social activities may help.
On the horizon
Researchers are developing a number of drugs that target chronic inflammation in hopes of reducing the risk of chronic diseases, especially cardiovascular disease. But inflammation?s complexity makes this a tricky task. Even if a drug lowers levels of certain inflammatory markers, that doesn?t necessarily mean there will be a benefit in terms of disease prevention or treatment. What?s more, since the inflammatory response is essential for survival, it would be risky to tamp it down too much.
