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Introduction to NF-κB

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that reads and copies the DNA (a transcription factor).

NF-kB is the single most important factor in causing inflammation in the body and virtually all popular herbs inhibit this protein complex (in many/most cells of the body).  Other proteins that are very popular in the literature are the cytokines TNF, IL-1, and IL-6, but NF-kB largely controls the production of these and other cytokines.

NF-κB is activated in response to stress, cytokines (like IL-1b [R] and TNF), free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral infections,  cocaine, and ionizing radiation.  See a full list below.  With cytokines, the effect is bi-directional, as it induces cytokines and is induced by cytokines.

Oxidative stress/ROS/Free radicals is an important inducer of NF-KB.

NF-κB plays a key role in regulating the immune response to infection.   Chronic activation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases.  Too little activation leads to susceptibility to viral infection and improper immune development.

NF-κB is a “rapid-acting” transcription factor, which means that it is present in cells in an inactive state and does not require new protein synthesis in order to become activated (other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors). This allows NF-κB to be a first responder to harmful cellular stimuli.

Many bacterial products and stimulation of a wide variety of cell-surface receptors lead to NF-κB activation and fairly rapid changes in gene expression.  Pathogens activate NF-κB via Toll-like receptors (TLRs), which is important both innate and adaptive immune responses.

NF-kB, Health, And Performance

It’s important to realize that inflammation in one kind of cell has somewhat different effects as inflammation in another type of cell.

Activating NF-kB in the body causes inflammation and growth and this is something we want to keep to a minimum to prevent chronic disease. However, inducing NF-kB in the brain can increase intelligence by growing neurons.

So occasional spikes of inflammation in the brain can be conducive to enhanced cognitive performance.   Acutely inducing NF-kB is one of the mechanisms by which LLLT enhances our cognitive function (note that this isn’t chronic activation).

Specifically, in the brain, NF-κB is responsible for growth and development and is important for synaptic plasticity, learning, memory, synapse function, and growth of dendrites and dendritic spines.  Some products from its activation are the Brain-derived neurotrophic factor (BDNF), Nerve Growth Factor (NGF), Cytokines (TNF) and Kinases (PKAc).

One potential downside to brain induction of NF-kB is anxiety [R], as mice who are deficient in this transcription factor have reduced levels of anxiety.   This could be the underpinning of a study that showed excessive worry/anxiety coevolved with intelligence in some people [R].

High IQ was associated with a lower degree of worry, but in those diagnosed with GAD, an anxiety disorder, high IQ was associated with a greater degree of worry [R] Just a thought.

Another potential downside if activated chronically is depression [R].

Therefore, for the brain, it’s better to be activated in bursts rather than chronically.

Stress activates NF-kB [R], which is why occasional, acute bouts of stress can be extremely beneficial to cognitive enhancement, but chronic stress is harmful, as it chronically activates this protein.

Acute exercise also activates NF-kB temporarily in muscle [R] (and other parts of the body), but, again, chronic and acute activation is different.  Exercise is generally very healthy when not overdone.

The same can be said about the sun, in that it activates NF-kB acutely and a small dose of sun is great but too much is harmful.

Like the brain, the heart responds in the same way.  Acute bouts of NF-kB induction can be beneficial to the heart, especially during a heart attack, but chronic activation will cause heart disease [R].

Eating too much, which causes weight-modulation/obesity, is known to cause a lot of health problems.  Obesity and overeating activate NF-kB [R], which explains why obesity is correlated with most chronic diseases.

Activation of Nf-kB in the hypothalamus can cause insulin and leptin resistance and overeat (via ER stress), creating a vicious cycle (eating causes Nf-kB, which causes more eating, etc..) [R].

But one must realize that the body is always involved in trade-offs.  When we eat too much and become fat the body realizes this and figures we need to expend this energy by growing, increasing metabolism, etc.. To to do this, it activates NF-kB, which is a master growth regulator in the body.  This in turns allows us to get thinner and expend energy and decrease our fat storage.

Indeed, NF-kB was found to promote energy expenditure and inhibit fat tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity [R].

But of course, this growth comes from our body’s inflammatory response and increases our risk for cancer and autoimmune disease.  Hence, the tradeoff.

Diseases Associated With Chronic NF-κB Activation

This is only a partial list.  Since NF-kB induces TNF, IL-1, and IL-6, it will contribute to all of the diseases associated with these cytokines.

Not associated with Autism [R].

NF-kB Inducers

NF-kB Inhibitors

Inhibiting NF-kB promotes antigen tolerance [R], which means it can reverse some food allergies/intolerances.

All because a substance inhibits NF-kB in one type of cell in the body, it doesn’t mean it’ll inhibit it in all cells.  For example, some of these substances inhibit NF-kB in most of the body but activate it in the brain.

Lifestyle/Foods

Most fruits and veggies will help inhibit NF-kB.

Top Supplements

Other Supplements

There’s much more that aren’t listed…

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

Disclaimer and Caveats

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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26 COMMENTS

  • Angel

    I’ve been suffering from debilitating chronic fatigue due to CFS / Fibromyalgia. Tired all the time and the worst about it is the shallow sleep. This article is pretty spot on with all the symptoms, my doctor did try to explain nf kappa b pathway, oxidative stress, ebb virus fever blah blah blah…which didn’t make much sense to me. To deal with this, he told me to get this anti fatigue supplement on Amazon (it’s called 8bioenergy). I’d add it to the list of top supplements here, it’s genuinely what’s really worked for me after trying melatonin, astragalus, magnesium, b12 etc etc. Thanks for this article, making it so much clearer to understand! Very interesting…

  • Joseph

    What about ashwagandha? Wouldn’t that inhibit it too?

  • Mr. sick

    Well would be nice to know which supps increase Nf-KB in the brain but decrease it elsewhere. To bad it’s not stated in the article.

    I wonder if Nf-KB is really 100% a bad guy. On the other posts, you always take an ambivalent look. You only mentiond a positive effect in 1 sentence, Is it really that rare that people who catch infection easily are lacking in Nf-KB?

  • Sharon K Campbell

    D-Mannose Powder binds bacteria and helps it leave your system. Good Luck!

  • Alyson

    I just found this page, and I realize the last post was years ago but maybe someone can help. I am experiencing Bladder Inflammation after two rounds of Cipro for a UTI. Something the doctors have said I need to “ride out”, its been just over a month. I have cut of alcohol (for the most part) and coffee, no citrus fruits. I have been taking Slippery Elm and Marshmallow Root every day, a probiotic, antihistamines when needed, and Ibuprofen. Just recently I started taking turmeric which is supposed to help with bladder inflammation. Any Inhibitors you can recommend that would benefit the bladder?

    1. Karen

      I personally would do research on side effects of Cipro. It is one drug I personally will never take again due to known harmful side effects. What a shame that our nation is quick to put meds on the market without long term studies, and slow to pull them off.

    2. Usama ghazi

      Go with an anti inflammatory diet first of all no gluten no dairy no sugars. Use regular anti histamines and ask ur doc for rx strength antihistamines. Shops I find helpful for my patients include OM3 fish oil; VIT D3; magnesium MALATE; vit b supercomplex; turmeric with curcumin and a good green superfood powder daily (like tree of life or green goddess brand for example. As a pain physician I then offer the patients a series of nerve blocks to pudendal, inguinal and genitfoegenitofemoralnerves x2-3 rounds every two weeks (if no effect love on to causal epidural combined with sympathetic nerve injections under xray by the spine. Of short term relief obtained with any injection but no lig term then move on to stem cell injections combined with pelvic floor therapy and biofeedback techniques.hope this helps. sincerely Dr Usama Ghazi (Denver CO). Find a local pain physician and ask for their input on these reps. They usually work. I see patients from all over the country for pelvic pain and these almost always work so find a local doc who can do these procedures (usually board certified pain physician)?!!! Best of luck to u!!

  • Haim Benchimol

    Sorry, I forgot some important ones: resveratrol from polygonum cuspidatum, 250mg were very effective. Also Luteoline was great and maybe above all others I found Epilobium Parviflorum to be really great, it’s an Onagraceae, it also fights mold strongly. I have to review my papers about it to put some references.

  • Haim Benchimol

    About a year ago, I had to do a deep investigation about this matter due to my loved dog having bladder cancer, which has a strong relation with NF-kB inflammation. After many trials, what I truly found to help where: honokiol (high doses, for his 25kg he needed 2g of honokiol), Yi Yi Ren (called Lacryma Jobis, this one, in extract form, was very effective), skullcap, ellagic acid with quercetin and 180mg artemisinin (along with a 40:1 whole herb extract).

  • deejayvj

    Wormwood/Arteminisin

  • Barry

    EGCG – epigallocatechin gallate – safety citations:
    Curr Pharm Des. 2013 ; 19(34): 6141–6147.
    For this, you get Polyphenon E and green tea extract maximum tolerated doses for patients but the data is buried in the body of the paper.

    Chow, H.H.; Cai, Y.; Hakim, I.A.; Crowell, J.A.; Shahi, F.; Brooks, C.A.; Dorr, R.T.; Hara, Y.;
    Alberts, D.S. Pharmacokinetics and safety of green tea polyphenols after multiple-dose
    administration of epigallocatechin gallate and polyphenon E in healthy individuals.
    Clin. Cancer Res. 2003, 9, 3312–3319.
    This paper is a direct study of 4 weeks of dosing with humans. It finds 400mg EGCG twice a day had no more side effects than the placebo group. Blood levels rise over the course of 4-weeks.

    There is a paper that shows that extremely high doses of EGCG in animals, 300mg/kg is toxic – this would be quite hard to obtain in humans. 15g per day for a 110lb person.

    There are also papers out there that demonstrate or hypothesize that empty stomach dosing, Vit C, black pepper increase the bioavailability of EGCG.

    Of course, experience will be individual.

  • Jane Woolley

    NF-kappab. Siri interfered with the last message

  • Jane Woolley

    What is your best advice for inhibiting Ng-Kaplan for chronic sinusitis with nasal polyps?

  • Jean
  • Thomas

    Have you ever helped anyone that had trouble getting good sleep from their nose becoming blocked? For a DIYer which of your articles would be the most beneficial, off the top of your head? Thanks.

    1. Jean

      Low histamine diet is critical. Rinse your nose with a neti pot before sleep. Make sure you sleep with an open window and make sure that you are not in contact with dust mites (put pillow in freezer). Then you can start with tinospora extract, intranasal LLLT, xylitol sinus care spray, pelargonium sidoides (umckaloabo) and maybe beta glucans.

  • Steve Michaels

    Put a warning sign on EGCG. I went to the ER the other day because of it. It definitely caused damage to my liver, I hope not to get scarring.

    Took 6g NAC over the next 2 days, along with 400 mcg selenium/day and 10g vitamin C. I also shot up a solution of B1, B6,B12 up my butt to make it work better.

    Stay safe,
    Steve

    1. Joe

      EGCG can cause liver damage if too much is taken – like 6 pills a day. 1 pill doesn’t do anything. You probably have an underlying issue or you were taking other things.

      How do you know you got liver damage?

  • mike

    What do you think of this site?
    http://immortallife.info

  • Alex

    Hi there! Is it typo or am I missing something: “Also, plant-based foods have phytic acid, which inhibits phytic acid”?

    1. Joe

      Lol,typo. Fixed.

  • Jean

    Benfotiamine is a great NF-KB inhibitor. Works great for me when I have high inflammation.

    1. Joe

      Thx

  • sam

    You list chocolate as an nf-kb inhibitor but as quite inflammatory in other papers. I’ve found chocolate to be inflammatory and causes me acne, but I love it… how would it inhibit nf-kb?

    1. Joe

      Some people have a sensitivity to it, such as myself.

      Please provide a source that it’s inflammatory.

      1. sam

        My experience, according to Hume, Kant, Einstein, is the source. The only thing that is certain is that empirical data. I consume it by itself and it causes my skin to become greasier and for pus to arise full of macrophages and other signs of inflammation.

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