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Inflammation – The Silent Killer

We are all familiar with the basic concept of inflammation, causing redness, swelling and pain. A bee sting, a cut or broken bone, are obvious examples of this short-term inflammation. When you heal the inflammation subsides. This is a beneficial process that recruits to the injury site immune cells to fight infection, healing proteins and enzymes to help break down damaged cells and rebuild the tissue. Medications are given to help deal with pain, antibiotics to prevent infection. In short, these obvious injuries call for intervention.

What about silent inflammation? This is a chronic, low-grade inflammation that exists to varying degrees in all of us without us being aware. Only if it becomes so severe it causes pain will we notice it. This slow, smoldering inflammation will edge us closer to disease every day it is undetected. As scientists now know, the more inflammation, particularly chronic inflammation, you have, the more rapidly your body ages. In fact, we know that almost all chronic diseases—from cancer, to arthritis, to heart disease, to diabetes, to Alzheimer’s disease—have one thing in common: destructive, unchecked inflammation.

Cancer, heart disease, Alzheimer’s, diabetes, stroke, kidney disease, arthritis, liver and lung disease. All of these chronic diseases of aging have a common root in inflammation, and the studies proving so roll out month after month, year after year. If you could identify your levels of inflammation and lower them, it would follow you would lower your risk of these major diseases. And there are verifiable ways to do both.

But first, what is silent inflammation? We start by looking at a quick overview of what causes this low-grade, chronic inflammation, as opposed to injury related acute inflammation.

One of the most common substances that cause inflammation is excess sugar. Elevated sugar damages cells, proteins and lipids in a process called glycation, where it destroys the delicate structures, rendering them unable to perform their normal functions. This is one of the ways we measure diabetes risk, or progression of diabetes using a blood test called HbA1c, or glycated Hemoglobin (part of red blood cells). Red blood cells live approximately 3 months, so an HbA1c measurement is the percentage of red blood cells damaged by sugar in the blood stream over a roughly 3 month period. The higher your average glucose levels, the higher your HbA1c number. In addition, excess sugar damages proteins and lipids, parts of every living cell. Immune cells called Macrophages, are notified that these distorted and damaged cells called Advanced Glycosylation End products (AGE’s), need to be destroyed. These AGE's trigger the inflammatory mediator NF-KB, which activates numerous inflammatory genes. I like to think of excess sugar in our bloodstream as “rusting from the inside out”.

 Sugar consumption over time

Very closely related to sugar excess, another low-grade inflammation source is white fat cells. With two-thirds of Americans overweight, this is also a major contributor to silent, chronic inflammation. Excess sugars are converted into fat molecules called Triglycerides, and are stored in adipocytes, a fancy word for fat cells. But daily overconsumption of sugars causes these fat cells to bloat and near bursting, as they were never designed to handle so much fat. The fat cells send out alarm signals to the immune system, which calls in Macrophages to attack the fat cells as if they were infective invaders. The resultant inflammation is daily and ongoing.

 Mitochondrial dysfunction

These cells stuffed with fats also have poorly functioning and defective mitochondria, which are supposed to oxidize and burn off this fat. Poorly functioning mitochondria also release excess free radicals, which damage delicate cell structures and create more inflammation.

Mitochondria

Mitochondrial dysfunction is common as we age, where the little powerhouses of our cells become less numerous, enlarged and less efficient. They create even more free radicals, which damage cellular structures, and start production of Inflammasome, which triggers other inflammatory cytokines. Unchecked, they promote cell death or even uncontrolled cell growth - cancer. 

These are some of the most common instigators of silent inflammation, but not all. Oxidized cholesterol is inflammatory and contributes to atherosclerotic plaques. Plaque build up sends inflammatory signals from the walls of your arteries, calling the immune cells again to the site of this inflammation, which in trying to clear plaque, create more inflammation. Homocysteine causes inflammation of endothelial cells, the delicate one cell lining of our arteries, whose health affects our blood pressure. Trans fats, artificial sweeteners, preservatives and smoking are just a few other inflammation causing substances or habits.

So if we all have a certain level of inflammation in our bodies, how much is too much? Is there any tests that can give us insight into the levels of this silent and dangerous inflammation?

There are, and it is a shame more doctors are not aware of the importance of monitoring these tests. They are not exotic tests, or even that expensive, and can give us some crucial information on our risks, so we can act to lower these levels through lifestyle actions and supplementation. Please keep in mind none of these tests are diagnostic of anything but inflammation. Do not play internet doctor and freak yourself out!

The most inexpensive, and broad based test to determine your silent inflammation is called C-Reactive Protein. It is a very accurate measure of systemic inflammation. It won't tell you where the inflammation is located, but that is not as important as knowing your levels. Even if you have no symptoms of disease, elevated CRP levels may signal an increased risk for practically all degenerative disorders, including cardiovascular disease, cancer, diabetes, and more.

When CRP binds to specific molecules in the body, it participates in rapidly raising the production of inflammatory signaling molecules called cytokines and other inflammatory mediators. However, when CRP rises unchecked, it can contribute to destructive chronic inflammationOptimal CRP levels for everyone to strive for are under 0.55 mg/L in men and under 1.0 mg/L in women. This is important to keep in mind because the laboratory reference range is 0.0-3.00 mg/L. It is important to know that you should avoid testing CRP levels if you are sick, recently injured, or have exercised strenuously in the preceding days. All of these situations will have caused an acute, or temporary spike in your CRP levels, obscuring your real levels of chronic low-grade inflammation. It is particularly effective in suggesting your cardiovascular and stroke risk. Elevated levels of C-reactive protein have also been found to be associated with risk of developing type II diabetes, loss of cognitive ability in seemingly healthy people, Alzheimer’s disease, and depression in the elderly. You can ask your doctor about having this test done, or just order this test from Life Extension without a doctors involvement, to be done at your local LabCorp, for only $42. There are some state restrictions, see here.

You can also test your TNF-a levels. Tumor Necrosis Factor alpha is a cell signaling cytokine involved in systemic inflammation. Those immune cells I have been talking about above, called Macrophages, are the primary producer of TNF-a. High levels may be seen in cases of sepsis, autoimmune disease, various infectious diseases, rheumatoid arthritis, inflammatory bowel disease and certain cancers. LabCorp uses 0.0-2.2 pg/mL as the reference range. The test is cheapest again, when ordered through Life Extension, where it costs $75. Once again, avoid testing TNF-a if you are currently sick or injured. 

Lastly, there is a test for levels of IL-6, or Interleukin-6, another inflammatory cytokine that is over-produced in the aged, which contributes to autoimmune disease, immune dysfunction, osteoporosis, breast cancer, B-cell lymphoma, and anemia. IL-6 also regulates the growth and differentiation of various types of malignant tumors, including prostate carcinomas; serum levels of IL-6 are elevated in patients with metastatic prostate cancer. IL-6 has been identified as an inflammatory cytokine that is likely to play a major role in Alzheimer’s disease. Elevated IL-6 levels are also associated with increased risk for heart attack and stroke, development of type II diabetes, and as a predictor for increased risk of disability and death. A 1999 study found that individuals with high levels of both IL-6 and CRP were 2.6 times more likely to die during the nearly five-year study period than those with low levels of both measurements of inflammation. This test also costs $75 when done through Life Extension. Avoid testing IL-6 if you are currently sick or injured. 

If I had to choose one, I would always choose C-Reactive Protein, as it is has the most clear correlation to systemic inflammation levels, and research showing elevated levels are associated with these chronic diseases of aging. At $42, it is within most people's budget to check it once a year and make lifestyle and supplement changes.

Lifestyle modifications to lower inflammation include a healthier diet, containing anti-inflammatory foods...like more fruits and vegetables, and less animal products, like meats (especially grilled), and dairy. Lot's of pure water and beneficial fats, like high quality fish oils, olive oil and nuts. Less refined grains, processed foods, canned foods (BPA), preservatives, artificial sweeteners, colors and flavorings (of which most are petroleum based). Exercise is good, as long as it is not too strenuous, which can actually cause inflammation. Even a couple of 30 minute walks a week has been shown to have a multitude of benefits. Sleep is crucial, and a good deep sleep, turn off the TV and phone. Lowering your stress levels by meditation, gardening, reading a book at a park...simplifying your life (thanks Thoreau!). 

Fortunately there are also natural ingredients that can be taken with good research showing their ability to lower CR-P and chronic inflammation levels. 

curcumin

Curcumina constituent of turmeric, has been studied in over 7000 published scientific articles and is known to modulate several important pathways including the ones involved in inflammatory processesCurcumin promotes your body's healthy response to inflammation by inhibiting key inflammatory factors such as NF-kappaB, a protein molecule that acts like an "on-switch" in genes that govern the body's pro-inflammatory responses. Curcumin has been shown to exert powerful inhibitory effects on NF-kappaB activation. Curcumin also inhibits the metabolism of arachidonic acid, as well as the activities of cyclooxygenase, lipoxygenase, and cytokines (interleukins and tumor necrosis factors). This is important, because when normal inflammation continues over time and becomes prolonged or chronic, it can cause a multitude of pathologies—including cancers. Over two thousand published studies have evaluated the effects of curcumin on many cancers—such as those of the breast, prostate, liver, skin, colon, and lung cancer—by interfering at every stage of the complex sequence of their development, progression, and spread. While anticancer drugs often weaken the immune system, curcumin modulates it, serving as an immune-restorer. Most of the small randomized controlled trials of curcumin have consistently shown patient improvements in several inflammatory diseases, including psoriasis, irritable bowel syndrome, rheumatoid arthritis, and inflammatory eye diseaseCurcumin is a powerful herb in lowering C-Reactive Protein, in one clinical trial of 117 patients in 2015, it lowered their C-RP levels over 6 mg/L! This result could get many from an elevated C-Reactive Protein number down into optimal levels.

Boswellia

Boswellia - It may surprise you that of the ten leading causes of death in this country—including heart disease, cancer, and diabetes—seven are linked to a single enzyme in your body. It's called 5-lipoxygenase or 5-LOX and in excess can create a cascade of dangerous inflammatory conditions throughout your body. Everyone is familiar with Cox inhibitors, but very few substances block the opposite pathway of inflammation, LOX. 5-LOX is the first enzyme in the metabolic pathway leading to the synthesis of leukotrienes, which are harmful inflammatory substances that scientists believe may have a direct influence on a number of disease processes. Hundreds of published studies connect leukotrienes to cardiovascular disease, cancer, arthritis, and breathing disorders such as asthma and chronic obstructive pulmonary disease (COPD). They have also been implicated in Alzheimer's, inflammatory bowel disease, and osteoporosis. Boswellia blocks production of these harmful leukotrienes by blocking the pro-inflammatory 5-LOX, and altering the expression of tumor necrosis factor-alpha (TNF-a), which also plays an important role in chronic inflammation. Through its action in blocking 5-LOX, boswellia demonstrates effects that may help combat cancer, atherosclerosis, and asthma by lowering systemic inflammation.

This chart shows how the COX-2 and 5-LOX inflammation pathways are inhibited by Curcumin and Boswellia, lowering the downstream inflammatory molecules that cause disease.

Inflammatory pathways

A convenient way to get both Curcumin and Boswellia into your daily diet is by obtaining Inflam-Alieve, which contains the best studied and most effective form of Curcumin. BCM-95 contains the beneficial oils of the Turmeric root and achieves 7 times the blood levels of Curcumin and black pepper (piperine). Inflam-Alieve also contains a powerful Boswellia extract, standardized to 65% Boswellic acids, and 4 additional anti-inflammatory herbs, Garlic, Horsetail, Stinging Nettle and Celery.

Fish Oil

Omega 3 Fish Oil - It is well known that a diet rich in omega-3s reduces the body's overall burden of inflammation, a fact that gained relevance as scientists discovered the growing role of chronic inflammation in causing the diseases (or symptoms) of aging. Fish oil works inside a cell to produce its anti-inflammatory effects. Small molecules called resolvins and protectins (think "resolve and protect") were discovered. Each of these molecules provides different but overlapping functions in actively resolving inflammation. First, they sent out a "stop signal," quickly putting a stop to runaway inflammation. Next, they triggered the active resolution of inflammation. In other words, having enough omega-3s in your system provides your body with the tools necessary to combat and resolve inflammation almost as soon as it is triggered. Fish oil has been shown effective at reducing the inflammatory cytokines that can cause metabolic syndrome, cardiovascular disease, lung disease (asthma & COPD), inflammatory bowel disease, rheumatoid arthritis, cognitive decline, and cancer. The association between greater fish oil/omega-3 consumption and reduced systemic inflammation is substantiated by data from several large observational trials. In 855 healthy participants from the Health Professionals Follow-Up Study, intake of omega-3 fatty acids was associated with lower plasma levels of markers of TNF-α activity. The Nurses’ Health Study I cohort of 727 women revealed lower concentrations of inflammatory markers (including CRP and IL-6) amongst those in the top 20% of omega-3 consumption, when compared to those who consumed least amount. In the ATTICA study of over 3000 Greek men and women without any evidence of cardiovascular disease, participants who consumed over 300 g of fish per week had, on average, 33% lower CRP, 33% lower IL-6, and 21% lower TNF-α than participants who did not consume fish. In a sample of 5,677 men and women without cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, long-chain omega-3 intake (from fish or supplements) was associated with reduced plasma concentrations of multiple inflammatory markers (including CRP, IL-6, and TNF-α receptor, a measure of TNF-α activity).

Vitamin D

Vitamin D - Vitamin D appears to exert anti-inflammatory activity by the suppression of pro-inflammatory prostaglandins, and inhibition of the inflammatory mediator NF-κβ. Studies suggest vitamin D deficiency may promote inflammation. Vitamin D deficiencies are more common amongst patients with inflammatory diseases (including rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and diabetes) than in healthy individuals. They also occur more frequently in populations that are prone to low-level inflammation, such as obese individuals and the elderly. Vitamin D levels can drop following surgery (a condition associated with acute inflammation), with a concomitant rise in CRP. Low vitamin D status was associated with increased inflammation and elevated CRP. 

So now you have a basic understanding of silent inflammation and it's destructive long term effects increasing your risk of chronic disease. You also have some lifestyle modifications and supplements to start on to immediately begin lowering the danger posed by neglected inflammation. Lowering your risk of cancer, heart disease, Alzheimer's, lung disease, inflammatory bowel disease by taking these few steps is the best gift you can give to your health! 

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