Inflammation – A Central Driving Factor Screwing Up Your Health

For those of you suffering with a chronic health problem, you’ve probably ran across inflammation before. A vast majority of patients in my office struggle with autoimmune and/or CIRS (Chronic Inflammatory Response Syndrome). Simply put, inflammation contributes to the destructive breakdown of your body and prevents your cells from healthy function. Chronic health problems (heart disease1, joint pain, chronic fatigue, autoimmune diseases, depression, and fibromyalgia) have inflammation as a driver preventing you from getting better. If inflammation is such a problem, what causes this inflammation in people?

NF‐kappa B – The Inflammation Megaphone

Inflammation Megaphone

Inflammation is like a megaphone. It takes any subtle symptom you have and increases its intensity.

One of the strongest drivers of the inflammatory cascade is the cytokine NF‐kB. NF‐kappa B is a key cytokine responsible for the amplification of the inflammatory process.2 Think of NF‐kappa B like a giant megaphone signaling the rest of your immune system to jump on board and start the entire inflammatory process. NF‐kappa B goes directly to your DNA and activates genes to promote the immune system. This leads to increased production of inflammatory chemicals. (If you want the nerd talk the inflammatory chemicals are IL‐6, CRP, Cyclooxygenase 2, prostaglandins, leukotrienes, inducible Nitric Oxide, TNF‐alpha, and cell adhesion molecules3.) I could (and probably will in the future) write an entire blog article on each of those inflammatory compounds individually. Those are some of the big players in health for chronically ill people, and this won’t be the last time you hear about them. These chemicals are implicated in pain, anxiety, depression, autoimmune diseases, fatigue, and a host of other complaints, but remember NF‐kappa B turns them all on!

What stimulates the production of NF‐kappa B?

Since we know inflammation is such a critical factor in helping patients, a key question is what is driving the inflammation? Certainly a diet high in processed food contributes to inflammation for many Americans. For example a single meal of egg and sausage muffin sandwiches with 2 hash browns caused an increase of 150% of NF‐kB for approximately 2 hours and increase in CRP4. Besides processed food, here is a list of stimuli that activate NF‐kB according to a study published in 1997 in the New England Journal of Education.

1. Inflammatory Cytokines: (TNF‐a, IL‐1B, IL‐17)
2. Oxidants (Free radicals)
3. Viruses (Rhinovirus, influenza, Epstein‐barr, cytomegalo, adenovirus)
4. Ultra Violet Radiation
5. Cortisol
6. Lipopolysaccharide (LPS from Gram Negative bacteria in the gut). 5

If you have an inflammatory condition, are you being checked for all these things? Are you doctors looking at oxidative damage from free radicals, toxic metals, chronic viral infections or re‐activations, stress and cortisol, gut dysbiosis like yeast infections, SIBO, and parasites? Getting to the bottom of these driving factors for your health problem is key to restoring your health. As a functional medicine practitioner I spend a ton of time with my patients addressing which of these issues contribute to their individual case. If you haven’t found someone who can evaluate these different drivers for you I highly encourage you find a functional medicine doctor who can.

NF‐kappa B is like a wild fire, it can promote itself!

Inflammation Fire

Inflammation is like a wild fire. Once it gets going it can keep itself going unless we intervene to put it out.

While there are many health imbalances that can drive inflammation did you catch the number one category on the list? A cause many people forget about is inflammation can self‐promote more inflammation! Think of inflammation like a fire. While a fire can have many different original causes (matches, lightning, unattended camp fire) once the fire is going it can just feed itself! We come across many patients that miss this. Their chronic inflammation is like an out of control wild fire, and by the time they come into the office the fire is feeding itself!

Putting out the fire: Turmeric and Resveratrol

One of my most common tools for helping patients quench an out of control inflammation fire is the combination of turmeric and resveratrol. While these are not new compounds there are a few little details that can make a big difference.

1. Turmeric is very poorly absorbed in humans. Even doses as high as 2,000mg show no change in serum levels, but when combined with piper nigrum (black pepper) can show serum levels of the curcumin increase by 2,000%6. Basically if you are using turmeric I highly suggest it be a form that also has a small amount of piper nigrum in it as an activator.

2. Resveratrol also shown to decrease the expression of NF‐kappaB7, but combining resveratrol with curcumin can have greater effects than using them individually8. For this reason we most often use these compounds together for our patients.

The Autoimmune Explosion of the Immune System: TH17 and Nitric Oxide – a small, but key factor

For autoimmune diseases, one big player that NF-kappaB works with is the TH17 system.  The TH17 system is the chief way that autoimmune diseases  cause self-tissue destruction. As far as damage goes, this part is the big damage dealer. TH17 uses nitric oxide to cause massive cell destruction. There are three different forms of nitric oxide enzymes and they are the following.

  1. Inducible Nitric oxide synthase (iNOS) = creates autoimmune destruction
  2. Endothelial Nitric oxide synthase (eNOS) = beneficial cardiovascular effects
  3. Neuronal Nitric Oxide synthase (nNOS) = beneficial nervous system effects

In order to help autoimmune patients, this has been one of the best systems to aim at for quickly decreasing the immune system destruction. A nice side effect is that some compounds can lower the iNOS, while raising the other two forms of NOS creating beneficial effects for the cardiovascular and nervous system. Compounds to support the TH17 system are:

  • Niacin
  • Huperzine
  • Vinpocetine
  • Resveratrol
  • Turmeric

These nutrients can be a key, short term factor for helping patients decrease their immune system inflammation.

In Conclusion: CRP is a good test for inflammation, but not perfect.

If you suffer with a chronic health problem consider inflammation as a central piece to your puzzle for health. The blood test CRP is considered the “gold standard” for inflammation. If you have not had this tested and you suspect inflammation it is an absolute must! We consider anything above 3 elevated (or 0.3 depending on which units your lab uses). However, be careful not to write off inflammation as a problem for you if the CRP test is within normal ranges. Just because CRP is low that does not mean other inflammatory markers (like NFkappaB) are ok! In fact some of my most dramatic results in patients have been with people who have previously been told they have “no inflammation” in their body because the CRP test was within normal. Once we used turmeric and resveratrol to put out the inflammation fire they found their health improved dramatically as their body was finally able to heal like it was designed to do.

Thank you for reading and I’ll see you next time!

Dr. Kyle Warren, DC

Want to learn more about autoimmune disease from Dr. Warren? Click the link below to read more!

Autoimmune Disease: How to Approach Fixing Them

1 Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci USA. 2004. Apr 13;101(15):5634‐5639

2 Tak PP, Firestein GS. NF‐kappaB: a key role in inflammatory diseases. J Clin Invest. 2001;107(1):7‐11

3 Vasquez Alex, Reducing Pain and Inflammation Naturally – Part IV: Nutritional and Botanical Inhibition of NFkappaB, the Major Intracellular Amplifier of the Inflammatory Cascade. Nutritional Perspectives: Journal of the Council on Nutrition of the American Chiroprctic Association. July 2005; 28(3):5‐12

4 Alijada A et al. Increase in intranuclear nuclear factor kB and decrease in inhibitor kB in mononuclear cells after mixed meal: evidence for a proinflammatory effect. American Clinical Nutrition 2004.

5 Nuclear factor‐kappaB: a pivotal transcription factor in chronic inflammatory disease. New England Journal of
Medicine.1997 Apr 10;336(15):1066‐1071

6 Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of
curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353‐6.

7 Manna SK, Mukhopadhyay A, Aggarwall BB. Resveratrol suppresses TNF‐induced activation of nuclear transcription factors NF‐kappa B, activator protein‐1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. Journal of Immunology. June 2000. 15;164(12):6509‐19.

8 Csaki C, Mobashen A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrol in human
articular chondrocytes: inhibition of IL‐1 beta‐induced NF‐kappaB‐mediated inflammation and apoptosis. Arthritis Res Ther 2009; 11(6):R165

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