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).
NF–κB 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–κB largely controls the production of these and other cytokines.
NF–κB 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 NF–κB.
NF-κB Function
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. 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.
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 NF–κB 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 NF–κB 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 NF–κB 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 NF–κB [5], which explains why obesity is correlated with most chronic diseases.
Indeed, NF–κB 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.
- Aging [7]
- Cancer – about 45 cancers [8]
- Autoimmune and inflammatory disease, Multiple Sclerosis [9], Lupus [10]
- Heart Disease, Atherosclerosis [11], Stroke[12], Angina [13]
- Diabetes [14] – Type 1&2 [15], Insulin resistance [16]
- Obesity [17]
- Pain [18]
- Anxiety [2], Depression[4], Schizophrenia [19], Bipolar (Anorexia?) [20]
- Gut diseases [21], IBS[22], Crohn’s [23], Colitis [23]
- Chronic Fatigue Syndrome [24]
- Arthritis [25]
- Migraines [26, 4], Headaches [21]
- Allergies [27], Asthma [28], COPD [29]
- Alzheimer’s [30], Parkinson’s [31], ALS [32]
- Osteoporosis [33]
- Sleep apnea [34]
- Eczema [35], Psoriasis [36]
- Kidney disease [37], Sarcopenia [38], HIV-1 activation [39], Sepsis [25], Gastritis [25]
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 NF–κB [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 NF–κB 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.
- Calorie restriction [66]
- Ketosis [67]
- Exercise [68]
- Mediterranean diet [69]
- Meditation [70]
- Yoga [71] (and increased activity of glucocorticoid receptor)
- Short bursts of stress/Glucocorticoids (exercise would work here) [72]
- Black Cumin Seed Oil [73]
- Blueberries [74]
- Fish/Fish Oil[75]
- Nutritional Yeast/B–glucans – found in mushrooms also [76]
- Resistant starch [77]
- Olive oil [78]
- Honey (gelam, but others as well) [79]
- Jasmine Tea/Tea Polyphenols [80]
- Rooibos tea [81]
- Tart Cherry [82]
- Cayenne/Capsicum [83]
- Pomegranate (Ellagic acid) [84]
- Stevia [85]
- Trehalose [86]
- Cinnamon/Sodium Benzoate
- Chocolate/cocoa [87]
- Soy [88]
- Flax [89]
- Sesame [90]
- Cruciferous veggies/Sulforaphane [91]
- Garlic (diallyl sulfide, S-allyl mercapto cysteine, ajoene) [92]
- Turmeric (curcumin) [93]
- Red pepper (capsaicin) [93]
- Clove (eugenol) [93]
- Ginger (gingerol) [93]
- Cumin [93]
- Anise [93]
- Fennel (anethole) [93]
- Basil [93]
- Rosemary (ursolic acid) [93]
- Olives
- Celery
- Tomato powder/Lycopene
Hormones
- Melatonin [94]
- Pregnenolone (Pregnenolone converts to other hormones that inhibit NF-kB)
- Progesterone [95]
- DHEA [96]
- Cortisol [97]
- Allopregnanolone [98]
- Estradiol [99]
Supplements
- Magnesium [43]
- Zinc [45]
- PQQ [100]
- Aspirin [101]
- Curcumin [102]
- Butyrate [103]
- NAD+ [104, 105]
- Lactic acid [106]
- Boswellia [107]
- EGCG [108]
- Theaflavins [109] (potent)
- Hydroxytyrosol [110]
- Licorice [111, 112]
- Luteolin [113]
- Andrographolide [28]
- Fisetin [114]
- Resveratrol [115, 104]
- Berberine [116]
- Theanine [117]
- Olive leaf/Oleuropein
- Parthenolide/Feverfew (potent) [118] – This is often used in the research literature to inhibit NF-κB, which means it’s likely potent and somewhat selective.
- Quercetin [114]
- Honokiol [119]
- Rutin [114]
- Myricetin [114]
- Bromelain [120]
- Chinese Skullcap/Baicalin [121]
- Danshen/ Tanshinone [122]
- Fo-Ti [123]
- Tribulus [123]
- Astaxanthin [124]
- Histidine [125]
- Betulin/Chaga [126]
- Oxymatrine [127]
- NAC [128]
- Lipoic Acid [129]
- Bilberry
- Astragalus
- Milk thistle/Silymarin
- Bitter melon
- Grape Seed Extract
- Epimedium
- Emodin (found in Fo-Ti, Resveratrol Pills, Aloe, Rhubarb)
- Ursolic acid
- Molecular Hydrogen [130]
