This month we highlight Inflammation and supplements that control or reduce it. Inflammation, oxidative damage and glycation damage are all related and intertwined in the impact they have on the aging process. Reducing one will generally improve the others, because whenever tissues of any kind are damaged in any way, the repair mechanism begins with local inflammation. If you are experiencing increasing blood sugar, worsening insulin resistance with higher sustained levels of insulin, the rate of ongoing damage will be in a constant climb, and you will consequently have higher levels of inflammation throughout your body.
Inflammation is the key initiating factor in major degenerative diseases. Some scientists estimate that inflammation underlies up to 98% of the diseases afflicting humans, including a vast array of seemingly different conditions such as cancer, heart disease, diabetes, and neurodegenerative disorders. Inflammation is also one of the mechanisms used by the immune system to fight invaders and heal injury, so it is almost as though the aging body increasingly sees its own tissues as an enemy or that there is a chronic state of injury that needs constant attention to promote healing. Regardless, inflammatory processes eventually become the source of much of the damage evident in the aging body.
Other authorities view the fact that inflammation generally rises with increasing age as a result of prior viral or bacterial infections, such as latent herpes that hide in the nerve cells, but periodically alarm the immune system into action or perhaps cause a low level of sustained immune activity. Still others see this tied to changes in diet and food quality in the last 100 or so years, particularly the changes in dietary fats and processed foods.
We talked above about elevated insulin as inflammatory, but there are several other known factors that promote inflammation. One prominent factor is nuclear factor-kappa beta or NFkB. NFkB is a protein that acts as a switch to turn inflammation on and off in the body. Scientists describe NFkB as a "smoke sensor" that detects dangerous threats like free radicals and infectious agents. In response to these threats, NFkB "turns on" the genes that produce inflammation. As we age, NFkB expression in the body increases, provoking widespread chronic inflammation and setting the stage for diseases ranging from atherosclerosis and diabetes to Alzheimer’s. Knowing this simple fact should motivate us to find ways to counteract NFkB’s deleterious effects and thus delay or avoid many of the diseases commonly associated with aging. Virtually all the measures cited in this article to lower NFkB reduce the other important causes of inflammation. In a recent article for Life Extension Magazine, Dr. Nicholas Perricone discussed the nature of low-level chronic cellular inflammation as the root cause of a multitude of maladies associated with aging, and as the primary cause of weight gain associated with aging. Below is a quote from that article ( or read the entire article) - a 'must read' if you want to understand how to effectively deal with inflammation.
THE MECHANISM OF A VICIOUS CYCLE
Damage to a cells plasma membrane starts a kind of domino effect that, in the end, causes a vicious cycle of increased inflammation. Here’s how it goes:
- The cell plasma membrane is made up of a double layer of fats called a “lipid bi-layer,” and this fragile film is easily and rapidly oxidized by the free radicals. This leads to the breakdown of the membrane that produces a substance known as "arachidonic acid."
- Arachidonic acid is further oxidized by enzyme systems to produce very active chemical products with pro-inflammatory activity such as "prostaglandins." Arachidonic acid can also leak into the interior of the cell and get into the mitochondria, the tiny furnace used for energy production.
- Arachidonic acid then disrupts energy production of the cell, which is critically needed for cellular repair.
- The fats in the cell plasma membrane can also become oxidized and mimic chemical messengers in the body, such as platelet-activating factor (PAF), which also triggers a series of inflammatory events on a cellular level.
- All of these events, cumulatively known as "oxidative stress," lead to increased production of free radicals inside the cell, with the activation of tiny messengers called transcription factors such as AP-1 and nuclear factor kappa B, or NfkB for short. When NfkB detects oxidative stress, it translocates to the nucleus of the cell, which contains the DNA (which in turn contains the master instructions of the cell). NfkB attaches to a portion of the DNA and instructs the cell to make inflammatory chemicals such as interleukins 1 and 6 and tumor necrosis factor, types of cytokines (intercellular chemical messenger proteins released by white blood cells as well as other cells) that create further inflammation and damage.
- When NfkB is activated in skin cells along with another transcription factor called AP-1, it can lead to wrinkles in the skin.
- When NfkB is activated in the brain, it can lead to Alzheimer’s disease, and activated in other organs it can lead to cancer.
- When NfkB is activated in the pancreas, it can lead to the destruction of the B-cells of the pancreas, which are the sole source of insulin, resulting in diabetes.
- NfkB blocks the ability to utilize insulin effectively, which leads to the storage of body fat, causing us to gain weight and have great difficulty shedding the pounds.
The message here is that chronic inflammation at the cellular level is the generating factor for much of what we observe as age-related functional decline and the diseases of aging. It is tied to oxidative and glycation damage, and is largely the result of dietary choices over a lifetime.
There are foods which are pro-inflammatory, and others which are anti-inflammatory. In the first of two previous articles of this series we talked about foods and supplements which prevent oxidative damage by virtue of having high levels of antioxidants. The second article laid out food and supplement choices to reduce damage from glycation. If you read those, you should now understand that minimizing chronic inflammation starts with eating to prevent these two forms of damage. [Part 1] [Part 2] The key nutritional factors are a diet rich in antioxidants, a balance of omega-6 to omega-3 fats of not more than 2-to-1, elimination of hydrogenated fats and trans-fats, eating small and frequent meals with low components of starches and sugars and higher levels of fiber.
But what if you have eaten all your life in a pro-inflammation manner; what beside diet can you take to put out the fire within? Since NfkB is the primary switch that turns up the heat you should start with supplements that quiet this signal chemical. In nature you find several foods with components that have been shown to inhibit the expression of NfkB or to block cytokines that result from its presence. These foods are the starting point for developing supplements consisting of food extracts in combinations that effectively down-regulate inflammation by blocking its primary driver.
Foods and food extracts that effect activity of NfkB
Turmeric (Curcuma longa) Curcumin is a compound found in a number of South Asian spices, most prominently in turmeric, a component of curry seasoning. Curcumin has well-established antioxidant and anti-inflammatory effects. That curcumin exerts these effects by inhibiting NFkB is becoming increasingly clear. Curcumin acts directly within the cell’s nucleus and also acts on substances that activate NFkB. For example, it binds iron and copper in brain tissue, reducing the activation of NFkB that is associated with the production of amyloid beta proteins in Alzheimer’s disease. It has been shown to inhibit NfkB in numerous cancer cell types in animal and human studies.
Licorice root extracts are among the oldest remedies in Chinese medicine, and have long been used for their anti-inflammatory, anti- viral, anti-ulcer, and cancer-preventive properties. More recently, scientists discovered that major components of licorice inhibited NFkB and protected rat liver cells from alcohol toxicity. Some components inhibit NFkB activation and decreased production of a pro-inflammatory cytokine in human colon cells, demonstrating how NFkB inhibition can interrupt the inflammatory cycle by which cytokines stimulate the production of still more cytokines.
Capsaicin, the main ingredient in red pepper, has both anti-inflammatory and anti-cancer effects. Red pepper compounds have long been used to manage inflammatory joint conditions. Capsaicin inhibits the induction of two inflammation-provoking enzymes in stimulated macrophage immune cells by preventing NFkB activation. Capsaicin also induces cell death in many cancers by modulating NFkB. Like curcumin, capsaicin inhibits the growth of adult T-cell leukemia cells by impairing NFkB activation. Capsaicin further impairs cancer progression by reducing levels of vascular endothelial growth factor, thus depriving growing cancers of nutrients.
Clove extract (eugenol) inhibits NFkB-mediated expression of inflammatory cytokines. Like capsaicin, eugenol inhibits NFkB activation in stimulated macro-phage immune cells, reducing their synthesis of COX-2 and inflammatory cytokines. Oil of cloves has been used in dental care for centuries, and eugenol is now widely used to promote healing and prevent excessive inflammation after root canal surgery.
Ginger extracts exert anti-inflammatory activity and stimulate cancer cell death by inhibiting NFkB. Ginger reduces expression of the key inflammatory enzymes COX-1 and COX-2. Topical application of ginger extract inhibits skin inflammation in a mouse model92 by inhibiting NFkB. A ginger extract was shown to enhance tumor cell death and down-regulate production of tumor invasion factors by preventing activation of NFkB.
Basil and rosemary extracts, which contain ursolic acid, reduce cancer cell proliferation and tumor progression through NFkB inhibition. By inactivating NFkB, ursolic acid prevents initiated cells from reproducing and also triggers tumor cell death. This compound further down-regulates molecules that are required for tumor invasion and metastasis. Ursolic acid works through its effects on NFkB to induce resting macrophage immune cells to participate in tumor cell destruction in the early stages of cancer. Ursolic acid derivatives that inhibit NFkB have been shown to suppress pro-inflammatory enzyme, reducing cardiac fibrosis (scar tissue) in the heart tissue of diabetic mice.
Garlic has now been shown to exert its anti-inflammatory and immunomodulatory effects by inhibiting NFkB. Garlic extracts lowered NFkB activity by up to 41% in human blood and kidney cells that had been exposed to an inflammation-provoking challenge, thus reducing the expression of certain cytokines. These effects may be linked to the observation that a garlic compound inhibits damage to endothelial cells lining blood vessels and reduces atherosclerotic changes.101 Garlic’s inhibition of NFkB leads to reduced production of chemicals that cause lipid peroxidation, and this could provide further protection from atherosclerosis. NFkB inhibition is credited for garlic’s ability to protect liver cells from auto-immune damage in an animal model, as well as induce cell death in leukemia.
Pomegranate fruit extract protects cells against the effects of ultraviolet B radiation by inhibiting ultraviolet light-stimulated NFkB activation. Pomegranate fruit extract also prevented chemically induced skin cancers in mice through NFkB-mediated effects on both cancer initiation and promotion. Blockade of NFkB by pomegranate fruit extract has shown promise in osteoarthritis by inhibiting the production of protein-digesting enzymes and inflammatory cytokines. Pomegranate wine reduced the activation of NFkB in vascular endothelial cells by inflammatory mediators or biomechanical stresses, thus protecting against atherosclerosis. This list is from an article on our site titled “What Is Nuclear Factor-Kappa Beta?”, by Julius G. Goepp, MD, . I have stripped out the references to make it more readable, but you can read the entire article for more information: NfkB Article
These extracts are the primary components you should look for in products for natural suppression of systemic inflammation. There are several other strategies to address inflammation, depending on the body structures involved. There are many other factors that promote specific inflammation and available supplements that reduce or eliminate these problems.
As I wrote this, the massiveness of the subject dawned upon me, and I realized I could only touch the surface without getting too long-winded. NfkB is so much at the heart of the problem that it made sense to start here, but next month we will address more aspects of this primary aging mechanism, with a mind to specific areas of inflammation such as arterial inflammation that leads to heart disease.
Good Living – Frank
