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inflammation

Accumulating evidence supports an association between depression and inflammation. Stock photo
C-reactive protein is an important biomarker

By David Dunaief, M.D.

Dr. David Dunaief

Many of us have inflammation in our bodies, inflammation that is a potential underlying cause for a great number of diseases. Can we demonstrate the level of inflammation by measuring it? The answer is yes.

One of the most widely studied biomarkers for inflammation is high-sensitivity C-reactive protein (hsCRP), also referred to as CRP. High sensitivity means that we can measure levels as low as 0.3 mg/L more accurately.

What is the significance of the different levels? In heart disease, individuals who have levels lower than 1.0 mg/L are in the optimal range for low risk of inflammation. Levels of 1 to 3 mg/L represent the average risk range, and greater than 3.0 mg/L is a higher risk profile. Above 10.0 mg/L is less specific to heart disease, although still related, but more likely associated with other causes, such as infection and autoimmune diseases (1, 2). This biomarker is derived from the liver.

CRP is not specific to heart disease, nor is it definitive for risk of the disease. However, the upside is that it may be helpful with risk stratification, which helps us understand where we sit on a heart disease risk spectrum and with progression in other diseases, such as age-related macular degeneration, diabetic retinopathy, depression and autoimmune diseases. Let’s look at the evidence.

Age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in patients over the age of 65 (3). Therefore, it is very important to help define risk stratification for this disease. In a prospective study, results showed that hsCRP levels were inversely associated with the risk of developing AMD. The group with an hsCRP greater than 3.0 mg/L had a 50 percent increased risk of developing overall AMD compared to the optimal group with hsCRP lower than 1.0 mg/L. But even more interestingly, the risk of developing neovascular, or wet, AMD increased to 89 percent in this high-risk group.

The significance of wet AMD is that it is one type of advanced-stage AMD that results in blindness. This study involved five studies where the researchers thawed baseline blood samples from middle-aged participants who had hsCRP levels measured. There were more than 2,000 participants with a follow-up as long as 20 years. According to the study’s authors, annual eye exams and lifestyle modifications, including supplements, may be able to stem this risk by reducing hsCRP.

These results reinforce those of a previous prospective study that showed that elevated hsCRP increased the risk of AMD threefold (4). This study utilized data from the Women’s Health Study, which involved over 27,000 participants. Like the study mentioned above, this one also defrosted blood samples from baseline and looked at follow-up incidence of developing AMD in initially healthy women.

The highest group had hsCRP levels over 5.2 mg/L. Additionally, when analyzing   similar cutoffs for high- and low-level hsCRP, as the above trial used, those with hsCRP over 3.0 had an 82 percent increased risk of AMD compared to those with an hsCRP of lower than 1.0 mg/L.

Diabetic retinopathy — a complication of diabetes

We know that diabetes affects approximately 10 percent of the U.S. population and is continuing to rise at a rapid rate. One of the complications of diabetes affects the retina (back of the eye) and is called diabetic retinopathy. This is a leading cause of vision loss (5). One of the reasons for the vision loss is macular edema, or swelling, usually due to rupture of tiny blood vessels below the macula, a portion of the back of the eye responsible for central vision.

The Diabetes Control and Complications Trial (DCCT), a prospective study involving over 1,400 Type 1 diabetes patients, showed an 83 percent increased risk of developing clinically significant macular edema in the group with the highest hsCRP levels compared to those with the lowest (6). Although these results were with Type 1 diabetes, patients with Type 2 diabetes are at equal risk of diabetic retinopathy if glucose levels, or sugars, are not well controlled.

Depression

Depression is a very difficult disease to control and is a tremendous cause of disability. If we can minimize the risk of complications and hospitalizations, this is probably the most effective approach.

Well, it turns out that inflammation is associated with depression. Specifically, in a prospective observational trial, rising levels of CRP had a linear relationship with increased risk of hospitalization due to psychological distress and depression (7).

In other words, compared to levels of less than 1 mg/L, those who were 1 to 3 mg/L, 3 to 10 mg/L and greater than 10 mg/L had increased risk from 30 to 84 to 127 percent, respectively. This study involved over 70,000 patients.

What can be done to reduce inflammation?

This is the key question, since we now know that hsCRP is associated with systemic inflammation. In the Nurses’ Health Study, a very large, prospective observational study, the Dietary Approaches to Stop Hypertension (DASH) diet decreased the risk of both heart disease and stroke, which is impressive. The DASH diet also decreases the levels of hsCRP significantly, which was associated with a decrease in clinically meaningful end  points of stroke and heart disease (8).

The DASH diet is nutrient dense with an emphasis on fruits, vegetables, nuts, seeds, legumes and whole grains and a de-emphasis on processed foods, red meats, sodium and sweet beverages.

Conclusion

As the evidence shows with multiple diseases, hsCRP is a very valuable nonspecific biomarker for inflammation in the body.

To stem the effects of inflammation, reducing hsCRP through lifestyle modifications and drug therapy may be a productive way of reducing risk, slowing progression and even potentially reversing some disease processes.

The DASH diet is a very powerful approach to achieving optimal levels of hsCRP without incurring potential side effects. This is a call to arms to have your levels measured, especially if you are at high risk or have chronic diseases such as heart disease, diabetes, depression and autoimmune diseases. HsCRP is a simple blood test with easy-to-obtain results.

References:

(1) uptodate.com. (2) Diabetes Technol Ther. 2006;8(1):28-36. (3) Prog Retin Eye Res. 2007 Nov;26(6):649-673. (4) Arch Ophthalmol. 2007;125(3):300-305. (5) Am J Ophthalmol. 2003;136(1):122-135. (6) JAMA Ophthalmol. 2013 Feb 7;131:1-8. (7) JAMA Psychiatry. 2013;70(2):176-184. (8) Arch Intern Med. 2008;168(7):713-720.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

Studies show that even moderate exercise can significantly lower mortality risk when compared with no physical activity at all.

Reducing inflammation is part of this process.

By David Dunaief, M.D.

Dr. David Dunaief

When asked what was more important, longevity or healthy aging (quality of life), more people choose the latter. Why would you want to live a long life but be miserable? Well, it turns out the two components are not mutually exclusive. I would like you to ponder the possibility of a third choice, “all of the above.” Would you change your answer and, instead of making a difficult choice between the first two, choose the third?

I frequently use the example of Jack LaLanne, a man best known for popularizing fitness. He followed and preached a healthy lifestyle, which included diet and exercise. He was quite a motivator for many and ahead of his time. He died at the ripe old age of 96.

This brings me to my next point, which is that the number of 90-year-olds is growing by leaps and bounds. According to the National Institutes of Health, those who were more than 90 years old increased by 2.5 times over a 30-year period from 1980 to 2010 (1). This group is among what researchers refer to as the “oldest-old,” which includes those aged 85 and older.

What do these people have in common? According to one study, they tend to have fewer chronic morbidities or diseases. Thus, they tend to have a better quality of life with a greater physical functioning and mental acuity (2).

In a study of centenarians, genetics played a significant role. Characteristics of this group were that they tended to be healthy and then die rapidly, without prolonged suffering (3). Another benchmark is the amount of health care dollars spent in their last few years. Statistics show that the amount spent for those who were in their 60s and 70s was significantly higher, three times as much, as for centenarians in their last two years (4).

Factors that predict one’s ability to reach this exclusive club may involve both genetics and lifestyle choices. One group of people in the U.S. that lives longer lives on average than most is Seventh-day Adventists. We will explore why this might be the case and what lifestyle factors could increase our potential to maximize our healthy longevity. Exercise and diet may be key components of this answer. Now that we have set the tone, let’s look at the research.

Exercise

For all those who don’t have time to exercise or don’t want to spend the time, this next study is for you. We are told time and time again to exercise. But how much do we need, and how can we get the best quality? In a 2014 study, the results showed that 5 to 10 minutes of daily running, regardless of the pace, can have a significant impact on life span by decreasing cardiovascular mortality and all-cause mortality (5).

Amazingly, even if participants ran fewer than six miles per week at a pace slower than 10-minute miles, and even if they ran only one to two days a week, there was still a decrease in mortality compared to nonrunners. Here is the kicker: Those who ran for this very short amount of time potentially added three years to their life span. There were 55,137 participants ranging in age from 18 to 100 years old.

An accompanying editorial to this study noted that more than 50 percent of people in the United States do not meet the current recommendation of at least 30 minutes of moderate exercise per day (6). Thus, this recent study suggests an easier target that may still provide significant benefits.

Diet

A long-standing paradigm is that we need to eat sufficient animal protein. However, there have been cracks developing in this façade of late, especially as it relates to longevity. In an observational study using NHANES III data, results show that those who ate a high-protein diet (greater than 20 percent from protein) had a twofold increased risk of all-cause mortality, a four times increased risk of cancer mortality and a four times increased risk of dying from diabetes (7). This was over a considerable duration of 18 years and involved almost 7,000 participants ranging in age at the start of the study from 50 to 65.

However, this did not hold true if the protein source was from plants. In fact, a high-protein plant diet may reduce the risks, not increase them. The reason for this effect, according to the authors, is that animal protein may increase insulin growth factor-1 and growth hormones that have detrimental effects on the body.

Interestingly, those who are over the age of 65 may benefit from more animal protein in reducing the risk of cancer. However, there was a significantly increased risk of diabetes mortality across all age groups eating a high animal protein diet. The researchers therefore concluded that lower animal protein may be wise at least during middle age.

The Adventists Health Study 2 trial reinforced this data. It looked at Seventh-day Adventists, a group whose emphasis is on a plant-based diet, and found that those who ate animal protein up to once a week had a significantly reduced risk of dying over the next six years compared to those who were more frequent meat eaters (8). This was an observational trial with over 73,000 participants and a median age of 57 years old.

Inflammation

You may have heard the phrase that inflammation is the basis for more than 80 percent of chronic disease. But how can we quantify this into something tangible?

In the Whitehall II study, a specific marker for inflammation was measured, interleukin-6. The study showed that higher levels did not bode well for participants’ longevity (9). In fact, if participants had elevated IL-6 (>2.0 ng/L) at both baseline and at the end of the 10-year follow-up period, their probability of healthy aging decreased by almost half.

The takeaway from this study is that IL-6 is a relatively common biomarker for inflammation that can be measured with a simple blood test offered by most major laboratories. This study involved 3,044 participants over the age of 35 who did not have a stroke, heart attack or cancer at the beginning of the study.

The bottom line is that, although genetics are important for longevity, so too are lifestyle choices. A small amount of exercise, specifically running, can lead to a substantial increase in healthy life span. While calories are not equal, protein from plants may trump protein from animal sources in reducing the risk of mortality from all causes, from diabetes and from heart disease. This does not necessarily mean that one needs to be a vegetarian to see the benefits. IL-6 may be a useful marker for inflammation, which could help predict healthy or unhealthy outcomes. Therefore, why not have a discussion with your doctor about testing to see if you have an elevated IL-6? Lifestyle modifications may be able to reduce these levels.

References: (1) nia.nih.gov. (2) J Am Geriatr Soc. 2009;57:432-440. (3) Future of Genomic Medicine (FoGM) VII. Presented March 7, 2014. (4) CDC.gov. (5) J Am Coll Cardiol. 2014;64:472-481. (6) J Am Coll Cardiol. 2014;64:482-484. (7) Cell Metab. 2014;19:407-417. (8) JAMA Intern Med. 2013;173:1230-1238. (9) CMAJ. 2013;185:E763-E770.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.