I think most of us typically think of inflammation as our body’s protective response to injury and infection. Without it, we’d be in serious trouble (unless we lived in a sealed bubble.)

If it were only that simple…

Inflammation comes in two categories, “acute” and “chronic.”

Acute Inflammation:

When our body is behaving properly, immune cells (white blood cells, macrophages, etc.) kick into gear when they detect oxidative stress, injury or infection in the tissues. These cells release a storm of inflammatory chemicals and proteins into the surrounding tissues and into the blood stream to:

• Destroy any foreign invaders (i.e. bacteria, viruses)
• Signal more immune cells to the area
• Dilate blood vessels to increase blood flow to the area (to enable the influx of immune cells, oxygen and nutrients)
• Trigger the growth of tissues and new blood vessels (to aid in tissue repair and supply nutrients to these tissues)

This process is called “acute” inflammation, and will resolve within hours-to-weeks after the infection is controlled or the injury is healed…unless it doesn’t…

Chronic Inflammation:

Whereas acute inflammation protects us from our hostile environment, “chronic” inflammation (a prolonged state of low-level, smoldering inflammation, lasting months-to-years) can hurt or even kill us. This difference is one of the most important discoveries of modern medicine. We now recognize that chronic inflammation is involved in the development and progression of almost every chronic disease…including cancer.

The role of chronic inflammation is particularly poignant in the autoimmune and chronic infectious diseases, where the involved tissues are flooded with persistent chemical and protein signaling to repair and grow.

Chronic inflammation can also significantly reduce your body’s sensitivity to insulin, leading to persistently elevated levels of blood sugar, increased production of insulin and insulin-like growth factor 1 (IGF-1), metabolic syndrome, type 2 diabetes and obesity. All of these factors have been shown to increase the risk of cancer development, progression and recurrence.

The “Inflammasome”

Most of us have never heard of “inflammasomes” before, as they were discovered relatively recently (in 2002.) These protein complexes are an integral part of our body’s immune system. They are comprised of special, ‘danger sensing proteins’ that are activated by viruses, bacteria, and free radical chemicals.

Once activated, the inflammasomes signal our immune cells (macrophages) to begin to produce a storm of inflammatory proteins. The latest research indicates that inflammasomes are responsible in large part for the chronic inflammatory state that results from obesity.

The Role of Nuclear Factor Kappa-B (NF-kB) in Cancer

When immune cells first detect any signs of tissue injury or stress, they activate a cellular protein, called nuclear factor kappa-B (or NF-kB.) This protein is the main ‘switch’ that turns on the inflammation in the tissues. Activated NF-kB signals the cell (via many pathways, including through the activation of inflammasomes) to begin to produce numerous proteins involved in inflammation and tissue repair.

So far so good, as long as the growth signals are not happening in precancerous or cancerous tissues…

During chronic inflammatory conditions, inflamed tissues are predisposed to developing and accumulating DNA damage at a greater rate than non-inflamed tissues. This is due to the production of large amounts of free radicals in inflamed tissues [in fact, billions of DNA mutations develop in our cells each day as a result of free radical injury and toxic exposures.] When these highly-reactive chemicals interact with DNA, they can create DNA mutations. As long as the cell is able to either repair these DNA mutations (most cells have built-in DNA repair mechanisms) or signal the cell to undergo a process of cell suicide (“apoptosis”), precancerous cells will not develop.

However, during constant exposure to NF-kB directed signals (which happens during chronic inflammation), both apoptosis and DNA repair mechanisms are shut down. This leads to an accumulation of cells with genetic mutations. If these cells develop enough mutations, they can transform into precancerous cells and, eventually, cancer cells.

In the presence of chronic inflammation, precancerous and cancerous tissues are signaled to divide, grow and even invade into surrounding tissues (including blood and lymph vessels, which gives them access to the rest of the body; this is referred to as “metastatic” spread.) These inflammatory signals also inactivate immune cells in the area, preventing them from being able to identify and attack the newly formed cancer cells.

One of the sneaky things that cancer cells learn to do to ensure their own growth and survival, is that they can activate their own NF-kB. This enables them to turn on all of the same inflammatory proteins in the surrounding tissues, thereby hijacking the body’s tissue repair and growth mechanisms.

Experiments have shown that inflammasome activation involves NF-kB through a multi-step process. When the immune cells (macrophages) identify any tissue injury or oxidative stress, they first activate NF-kB. Activated NF-kB then signals the cells to form inflammasome protein complexes (steps 1 and 2), which are now ready (or ‘primed) to further respond to the tissue injury or oxidative stress. At this step (step 3), the activated inflammasome signals the cell to produce and release inflammatory protein (i.e. IL-1, etc.)

What Are Ways To Reduce Chronic Inflammation?

Since NF-kB is the main ‘switch’ in promoting inflammation, it makes sense to focus on this target.

Prevent NF-kB activation by preventing or minimizing conditions that activate NF-kB (i.e. tissue infection, injury and oxidative stress):

1. Prevent and treat chronic infections
   • Helicobacter pylori (gastric MALT lymphoma)
   • Hepatitis B and C (liver cancer)
   • Human papilloma virus (cervical, anal, vulvar and head and neck cancers
2. Avoid exposures to toxins
   • smoking
   • toxins in our food (environmental toxins, chemical food additives)
   • toxic household and personal products
3. Reduce oxidative stress
   • Consume foods (or supplements) that are rich in various antioxidants:
     • Alpha-lipoic acid
     • Coenzyme Q10
     • Curcumin
     • Green tea (EGCG) and other flavonoids and polyphenols
     • Folic acid
     • Garlic
     • Selenium
     • Vitamins C and E
   • Reduce your consumption of highly caloric meals (even eating too many calories of “healthy” food at each meal is inflammatory)
   • Reduce consumption of inflammatory fats, such as saturated fats, omega-6 fatty acids, synthetic hydrogenated (trans)fats
     • Limit your intake of corn oil, sunflower oil, soybean oil, safflower oil, margarine, non-organic animal fat
   • Increase your consumption of omega-3 fatty acids
     • Increase your intake of fish, grass-fed and organic animal products, flaxseeds and oil
   • Limit or avoid alcohol consumption
   • Limit or avoid your consumption of foods (particularly meats) that are prepared with high-heat (dietary advanced glycation end products)
   • Prevent or treat elevated LDL cholesterol (oxidized low-density lipoproteins are a key factor in the development of atherosclerosis and systemic inflammation)
   • Maintain a healthy body mass index (fat tissue produces numerous inflammatory proteins and free radicals)
   • Avoid disruption of night-time sleep (i.e. night shifts, exposure to light at night)
   • Avoid over-exercising (exercise reduces tissue oxidative stress, unless it is done to the extreme)
     • Exercise (moderately) at least 150 minutes each week, if possible
   • Reduce emotional stress
   • Treat low sex hormone levels (This is an area of controversy between conventional physicians and those who practice “functional medicine.” Studies indicate higher levels of oxidative stress among individuals with low testosterone, estrogen and DHEA)
   • Minimize exposure to ionizing radiation (i.e. ultraviolet light, CT-scans, X-rays, radiation therapy)

NF-kB inhibitors act directly on this protein to prevent it from becoming activated:

Food and nutrient NF-kB inhibitors (these directly inhibit NF-kB and reduce levels of oxidative stress, thereby reducing NF-kB activation)

1. Curcumin
2. Omega-3 fatty acids
3. Soy isoflavones
4. Licorice root
5. Capsaicin
6. Ginger
7. Pomegranate and berries (anthocyanidins)
8. Garlic
9. Green tea (EGCG) and other polyphenols and flavonoids
10. Vitamin D (also interacts with other proteins that inhibit the activation of the inflammatory cascade)
11. Zinc
12. N-acetyl cysteine (NAC)
13. Boswellia

Anti-inflammatory inhibitors downstream from NF-kB:

If you don’t block it at it’s origin (at or before NF-kB activation), there are still ways to block the cascade of events downstream before inflammation develops.

Natural compounds and pharmaceutical anti-inflammatory medications that block the key downstream enzymes that lead to inflammation. These include the cyclooxygenases (COXs) and lipoxygenases (LOXs).

1. Non-steroidal anti-inflammatory drugs (NSAIDs)
   • Examples: Aspirin, ibuprofen (Advil), naproxen (Aleve)
   • Blocks COX-1 and COX-2 enzymes
   • Side effects: gastric ulcers and gastritis (associated with chronic use)
2. Selective COX-2 inhibitor drugs
   • Examples: celecoxib (Celebrex), rofecoxib (Vioxx)
   • Blocks COX-2, only
   • Side effect: heart attack (rare)
3. Foods and nutrients that block COX 1 and COX-2
   • Curcumin
   • Omega-3 fatty acids
   • Resveratrol
   • Green tea (EGCG) and other polyphenols and flavonoids
   • Bee propolis
   • Milk thistle (silymarin)
   • Boswellia
   • Bromelain 

Testing for Systemic Inflammation

Most conventionally trained physicians do not assess systemic inflammatory serum markers in their day-to-day practice, as they are considered non-specific (many conditions can lead to ‘above normal’ levels.) Nevertheless, I believe that they can be generally helpful in determining if anti-inflammatory lifestyle changes and interventions are having a positive effect.

The following two blood tests are inexpensive and are good markers of systemic inflammation:

1. High-sensitivity C-reactive protein (CRP)
   • Optimum levels in males: Under 0.55 mg/L
   • Optimum levels in females: Under 1.50 mg/L
2. Fibrinogen
   1. Optimum levels: 200 – 300 mg/dL