Fighting Inflammation by Inhibiting NF-KB

Where there’s aging, there’s also chronic inflammation.

The relationship is so close that scientists have coined the term inflammaging.^1-3

It refers to the chronic, low-grade inflammation that occurs as we grow older, and contributes to the development of age-related disorders.

If we can stop this type of inflammation, we can slow and help reverse a major cause of degenerative aging.

Studies have uncovered one key factor: a gene-regulating protein complex called:

Nuclear Factor kappa B (NF-kB)

NF-kB is a primary driver of inflammation in the body. Inhibiting production of NF-kB can prevent inflammation.

No safe and reliable drugs can do that.

But a variety of currently available nutrients can.

By inhibiting cellular NF-kB, you have the capacity to slow down inflammaging.⁴

Numerous studies published in 2018 alone show that NF-kB-inhibiting nutrients can help fight the following aging factors:^4-14

• Insulin resistance
• Brain cell degradation
• Cancer development
• Heart muscle alterations
• Asthma
• Poor wound healing
• Arthritis

This is only a partial list.

The discovery that we can inhibit NF-kB means we’re gaining ground on slowing degenerative aging in a practical way.

How NF-kB Promotes Inflammaging

Inflammation in cells and tissues has a common pathway: activation of nuclear factor kappa B (NF-kB).

“Nuclear” in this case refers to the nucleus of the cell, where chromosomes carry genetic information that influences NF-kB.

When NF-kB gene expression signals move into a cell’s nucleus, it activates pro-inflammatory signals called cytokines.

These cytokines travel through the circulatory system to trigger inflammatory changes in tissues everywhere in the body.

Inflammation promotes diseases through an array of biochemical pathways. Inflammation has even been shown to shorten telomeres, (repetitive nucleotide sequences at the ends of chromosomes).

When telomeres shorten, cells eventually stop functioning, directly contributing to shortened cellular lifespans.^15-18

Increased levels of chronic inflammation induces destructive processes inside cells, rapidly producing still more NF-kB activation and an accelerating cycle of inflammation. This results in cell death, tissue loss, DNA damage, and other harmful changes that come with aging.^7,17-19

The good news is this cycle can be partially stopped. While NF-kB activation promotes inflammaging, blocking NF-kB inhibits inflammaging.

A group of nutrients, long ago available in supplement forms, have shown the ability to inhibit NF-kB.²⁰

Curcumin: Grandfather of NF-kB Inhibitors

The turmeric-derived compound curcumin is among the oldest-known NF-kB-inhibiting nutrients. More than a thousand studies have been performed on it, most since 2007.

Studies show that curcumin’s NF-kB-inhibiting properties may help prevent and treat cancers, including chronic lymphocytic leukemia, pancreatic cancer, liver cancer, and some pre-malignant conditions (when combined with conventional therapies).^21-24

In one finding, curcumin’s NF-kB blockade directly led to selective depletion of cancer stem cells in a lab model of liver cancer.²⁴ Cancer stem cells retain primitive survival characteristics, often resisting chemotherapy and re-emerging after treatment. This is a major cause of post-therapy cancer recurrence, so getting rid of cancer stem cells is critical for long-term, complete responses or remissions.

Another study revealed that curcumin can sensitize liver cancer cells to radiation treatment through reduction of NF-kB, with the potential for lowering radiation doses.²⁵

Curcumin’s NF-kB-inhibiting benefits go beyond fighting cancer. In metabolic diseases (obesity, diabetes, metabolic syndrome), fat tissue pumps out inflammatory cytokines. Animal models show that by inhibiting NF-kB, curcumin protects liver tissues from fat deposition and prevents progression of fatty liver disease to non-alcoholic steatohepatitis (a precursor of cirrhosis and liver cancer).²⁶

In rats fed a high-fructose diet (a guaranteed way to produce metabolic abnormalities), curcumin treatment reversed insulin resistance. It also lowered blood sugar, cholesterol and triglycerides, and a host of markers of fat-induced inflammation.²⁷

Individual animal studies now indicate promise for curcumin in preventing many other NF-kB-associated ailments, including:

• Toxin-induced liver damage,²⁸
• Colitis (inflammation of the colon, a precursor of colorectal cancer),²⁹
• Stroke-induced brain damage,³⁰
• Lumbar disc degeneration,³¹
• Obesity-induced, fatty acid damage to heart muscle and resulting fibrosis,³² and
• Severe, acute pancreatitis.³³

Curcumin is one of the most important NF-kB-inhibiting natural compounds.

Fish Oil Fights Inflammation

A 2016 study demonstrated that regular fish consumption lowered the risk of dying by 11%.³⁴

This helps support the idea that reducing inflammation can lead to improved longevity. And fish oil (rich in omega-3 fatty acids) has a compelling track record as an anti-inflammatory, with potent impact on NF-kB.^35,36

The NF-kB-inhibiting properties of fish oil and omega-3 fatty acids are important in preventing the blood vessel inflammation that contributes to formation of atherosclerosis.

Studies in cell cultures show that by inhibiting NF-kB, the omega-3 fatty acid known as EPA significantly reduces the degree to which blood cells stick to vessel linings, an important early step in plaque formation that leads to artery blockages.³⁷

Diabetes and obesity are major dementia risks, largely due to the chronic neuroinflammation to which they are linked.³⁶ In a mouse model of neuroinflammation, supplementation with two omega-3 fatty acids, EPA and DHA, inhibited NF-kB and sharply suppressed brain cell inflammatory responses.³⁶

Another metabolic disorder that can accompany obesity is non-alcoholic fatty liver disease (NAFLD). This can eventually progress to non-alcoholic steatohepatitis (NASH), an inflammatory condition that is a major cause of cirrhosis and liver cancer, and one of the main reasons for liver transplants in the U.S.³⁸

Animal studies reveal that omega-3 supplementation in mice fed a high-fat diet can prevent accumulation of liver fat and suppress markers of inflammation—again, through inhibition of NF-kB.³⁹

Inflammatory bowel disease (IBD) is another potentially deadly condition affecting millions of Americans.⁴⁰ IBD can lead to colorectal cancer and may require removal of substantial sections of the bowel. But animal studies show that omega-3 fatty acids can augment standard therapy by reducing NF-kB activation, an effect which has also shown promise in reducing colon cancer risk.^35,41

Researchers are constantly making new discoveries about the beneficial properties of fish oil. One exciting area of study is the involvement of specialized biochemical mediators derived from fish oil called resolvins. Resolvins are remarkable because rather than inhibiting inflammation, these intriguing biochemical factors promote resolution of inflammation including reduction of NF-kB.^42,43

In a clinical trial in obese women, an increase in resolvins was associated with the improved resolution of a range of inflammatory markers.⁴² This effect could reduce the risk of pro-inflammatory effects on the cardiovascular system related to obesity.

Fish oil and omega-3s have demonstrated, in clinical and animal models, inhibition of NF-kB in several serious conditions:

• Osteoporosis,⁴⁴
• Leukemia,⁴⁵
• “Dry” age-related macular degeneration, a major cause of vision loss in older people, and⁴⁶
• Severe, acute pancreatitis.⁴⁷

Consuming fish oil is clearly an important way to control NF-kB and improve health—but the source of the fish oil matters.

Lipoic Acid and NAC Lower NF-kB Levels

Oxidative stress in the body stimulates the activation of NF-kB, which leads to harmful inflammation.

Two compounds, lipoic acid (LA) and n-acetyl cysteine (NAC), have the ability to prevent oxidative stress and damage.^48-50 They do this by scavenging cellular toxins—particularly reactive oxygen and nitrogen compounds that tear at cell and mitochondrial membranes and damage protein and DNA molecules. By cutting off these stressors, both LA and NAC decrease cellular levels of NF-kB.^48,49,51

In animal research, alpha-lipoic acid has shown promise for alleviating metabolic abnormalities by reducing, through NF-kB inhibition, the amount and activation of inflammatory cells in fat tissue and artery-hardening plaque.^52,53

Alpha-lipoic acid also supported bone and joint integrity. It did this by preventing bone loss and NF-kB-induced inflammation and subsequent bone destruction in the joints of animals with experimentally induced arthritis. It also promoted new bone formation in a rat model of post-menopausal osteoporosis.^48,54

NF-kB inhibition and the resulting reduction in inflammatory cytokines and protein-melting enzymes are also credited with preventing ultraviolet-light-induced degeneration of the cornea and conjunctiva of the eye in an animal model. These are vital steps in cataract prevention.⁵⁵

NAC has been shown in animal studies to quench NF-kB activation, thereby reducing experimentally induced autoimmune reactions, a model of inflammaging.⁵¹

In animal models of inflammation-driven liver injury, NAC prevented liver cell damage and enhanced availability of energy to healing liver cells.⁴⁹

In an animal model of Parkinson’s disease, NAC’s inhibition of NF-kB reduced the loss of important dopamine-receiving cells. The death or impairment of these cells through exposure to inflammatory alpha-synuclein is a hallmark of this chronic, neurodegenerative conditon.⁵⁶

In a study on elderly rats, the combination of three nutrients, alpha lipoic acid, NAC, and alpha-tocopherol (a vitamin E form), slowed brain aging by inhibiting NF-kB and reducing brain inflammation.⁵⁷

Anti-Inflammatory Effects of Reishi Mushrooms

The Reishi mushroom (Ganoderma lucidum) has been demonstrated to have anti-inflammatory properties.^6,58 Studies have found effects of Reishi components and extracts in models of inflammatory bowel disease, in which these compounds reduce the cell-to-cell signaling that promotes and sustains these serious and troubling conditions.^58,59

In cultured white blood cells from individuals with Crohn’s disease, Ganoderic acid derived from reishi mushrooms significantly decreased production of inflammatory cytokines.⁵⁹

Ganoderic acid also shuts down NF-kB in cancer cells, leading, through a complex signaling cascade, to the cells’ self-destruction by the protective process called apoptosis (or programmed cell death). This can prevent tumors from fully developing.⁸

Many other Reishi components have been found to exert chemopreventive effects in lung cancer, the leading cause of cancer deaths in both men and women.⁶⁰

Reishi mushrooms can also have an impact on the reduction of inflammation in blood vessel walls, a major cause of atherosclerosis and cardiovascular diseases. A study in mice showed that treatment with Reishi polysaccharide components reduced NF-kB-promoted inflammatory signaling in the smooth muscle layer of the aorta, an important first step in preventing plaque formation.⁶¹

Brain inflammation increases seizure risk in the short term and contributes to neurodegeneration over longer periods. Ganoderic acid A from Reishi mushrooms, applied to immune system cells (glial cells) from mouse brains, significantly dropped production of inflammatory cytokines through NF-kB inhibition.⁶ The effect is likely to reduce seizure risk and potentially prevent long-term neurodegeneration.

Other Plant Extracts That Inhibit NF-kB

Healthy plant foods form the basis of the best-proven disease-fighting diets. One reason may be their content of compounds (phytonutrients) with a proven ability to inhibit NF-kB.

Here is a short list of some common phytonutrient supplements now known to have NF-kB-inhibiting properties:

• Green tea and its primary polyphenol component, epigallocatechin gallate (EGCG), have chemopreventive activity. Studies highlight how these compounds block the inflammatory steps that promote cancer growth.^9,62-64 In a 2018 study, EGCG proved capable of ameliorating age-induced heart muscle enlargement and stiffening, important findings for heart disease prevention.¹⁰
• Cyanidin-3 glucoside (C3G) is a dark-colored polyphenol, found especially in dark fruits and berries. C3G has NF-kB-inhibiting properties. These effects show promise for prevention of cardiovascular disease (through reduction of inflammation-promoted endothelial dysfunction), inflammatory bowel disease, and retinal degeneration.^65-71
• Resveratrol is a polyphenol found in red grapes and wine, which has also been shown to prevent retinal degeneration in aging animals, thanks to inhibition of NF-kB.⁷² This property of resveratrol has also shown promise in patients with the inflammatory bowel disease ulcerative colitis, for which a dose of 500 mg/day improved quality of life and reduced disease activity.⁷³ The ability of resveratrol to favorably influence NF-kB signaling helps explain its ability to improve insulin sensitivity in lungs of high-fat-diet-fed mice, to prevent osteoporosis and osteoarthritis-like changes in rats, and to prevent thyroid cancer in rodents.^11,14,74,75

Summary

Inflammation is a double-edged sword. We need it to fight off infections and clean up at sites of injury or damage. But prolonged, unresolved inflammation promotes degenerative diseases and accelerates aging.

Fighting chronic, low-grade inflammation is a critical tool for slowing degenerative aging and mitigating—or preventing—its symptoms.

At the heart of inflammation lies the signaling molecule nuclear factor kappa B (NF-kB), which responds to stimuli outside of cells by migrating to the cell’s nucleus and turning on the genes that generate pro-inflammatory signals (cytokines and other molecules).

By inhibiting NF-kB activation, we can reduce harmful inflammation and decelerate many aging processes.

No safe and reliable drugs exist for that purpose. Fortunately, we can turn to some of the best-known, natural supplements for potent, safe NF-kB inhibition.

Examples abound, from turmeric-derived curcumin to cold water fish oils, lipoic acid and NAC, as well as familiar plant nutrients including green tea, dark berries, and resveratrol.

These non-drug compounds provide a powerful way to keep NF-kB in check—and protect against many of the adverse effects of aging.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

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