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All About NF-kB: Function, Inhibitors & Activators

Written by Joe Cohen, BS | Last updated:

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NF-κB is a critical inflammatory signal. Unhealthy behaviors activate it, while many herbs inhibit it. Find our complete list of NF-κB hacks here.

What is 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).

NFκB 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 NFκB largely controls the production of these and other cytokines.

NFκB is activated in response to stress, cytokines (like IL-1b [1] 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 NFκB.

NF-κB Function

NF-κB plays a key role in regulating the immune response to infection. Chronic activation of NFκB 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. This allows NFκB 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 NFκB via Toll-like receptors (TLRs), which is important both innate and adaptive immune responses.

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

Role in Intelligence

Activating NF-κB in the body causes inflammation and growth and this is something we want to keep to a minimum to prevent chronic disease. However, inducing NFκB 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-κB 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).

NF-κB Activation: Negative Effects

Anxiety and Depression

One potential downside to brain induction of NFκB is anxiety [2], 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 [3].

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 [3], just a thought.

Another potential downside if activated chronically is depression [4].

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

Metabolism

Eating too much, which causes weight-modulation/obesity, is known to cause a lot of health problems. Obesity and overeating activate NFκB [5], which explains why obesity is correlated with most chronic diseases.

Indeed, NFκB was found to promote energy expenditure and inhibit fat tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity [6].

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

Inflammation-Related Diseases Caused by Chronic NF-κB Activation

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

Not associated with Autism [40].

NF-κB Activators

  • Oxidative stress [41]
  • Psychological Stress [1]
  • Eating too much – too many carbs, fat or protein will activate NF-κB.
  • An unhealthy diet – fruits and veggies contain phytochemicals to inhibit NF-κB [42]. Minerals like Magnesium [43], Chromium [44] and Zinc [45] can inhibit NF-κB. Also, plant-based foods have phytic acid, which inhibits NF-κB [46].
  • High blood glucose levels [47] – usually because of high glycemic index foods [48]
  • Low active Vitamin D (1,25) [49]
  • Smoking [50]
  • Lectins like ConA [51] (found in legumes)
  • Circadian Rhythm Disruption [52]
  • Sleep deprivation [53]
  • Sun/UV rays [54]
  • Acute exercise [55]
  • Alcohol [56]
  • Excess fat in the blood [16] (from excess fat, carbs or fat tissue/obesity)
  • Obesity [16]
  • Excess saturated fat [57] (but not caprylic acid and lauric acid)
  • Heavy metals [58]
  • High protein diet (via IGF-1) [59]
  • Aldosterone [60] and AngiotensinII [61]
  • Goji Berries [62]
  • Reishi [63] – depends on the cells. It also inhibits it.
  • Lithium [64] (in intestinal cells)

Stressors

Stress activates NFκB [1], 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 NFκB temporarily in muscle [55] (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-κB acutely and a small dose of sun is great but too much is harmful.

NF-κB Inhibitors

Inhibiting NF-κB promotes antigen tolerance [65], which means it can reverse some food allergies/intolerances.

All because a substance inhibits NF-κB 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-κB in most of the body but activate it in the brain.

Lifestyle/Foods

Most fruits and veggies will help inhibit NF-κB.

Hormones

Supplements

Drugs

  • Statins [26]
  • Metformin [131]

Want More Targeted Ways to Combat Inflammation?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.

About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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