Inflammation: Its Surprising Role in Everything from Depression to Insulin Resistance

In the minds of many, inflammation often is associated with the pain and swelling that occurs after trauma, whether from a sports injury or a wound. However, scientists are beginning to realize that inflammation may actually be the cause behind a surprising number of conditions including Alzheimer’s, cardiovascular disease, hypertension, diabetes/insulin resistance, multiple sclerosis, cancer and depression. Even weight gain is now associated with inflammation. In fact, any condition with a modifier of “itis” at the end of the word (dermatitis, bursitis, colitis, sinusitis, etc.) is linked to inflammation.

Inflammation is an essential process. Without it, wounds would not heal. However, when inflammation continues unchecked a process that was designed to help the body heal actually becomes highly destructive. Various factors encountered in our modern day lifestyles, including poor diet, stress, lack of sleep and exercise, contribute to the ongoing inflammation that can lead to a number of diseases. Inflammation also accelerates premature aging and can sabotage the pursuit of healthy aging.

Cardiovascular Disease

When anything threatens the body’s health—from disease-causing germs to the build-up of fatty plaque in the walls of a heart vessel—the immune system sends in wave after wave of cells to swarm and destroy the invader. Scientists now theorize that when plaque deposits build up on the walls of arteries, it causes macrophages to perceive the plaque deposit to be a foreign invader, and therefore attempt to eliminate the cholesterol deposit. In the blood vessels, layers of these immune cells pile up, creating lesions that become increasingly unstable and may eventually break free, inducing a heart attack. This link between inflammation and blood vessel health may explain why half of all people who have heart attacks don’t have high cholesterol. Scientists now realize that inflammation plays an important part in the development of cardiovascular disease and that C-reactive protein (CRP), a measure of inflammation, is a predictor of heart disease.

Insulin Resistance, Diabetes and Weight Gain

Scientists suspected a link between inflammation, insulin resistance and diabetes as far back as the early 1900s, when they gave diabetes patients aspirin-like compounds known as salicylates and found that these anti-inflammatory compounds reduced blood sugar levels. However, the high doses necessary to produce an effect caused ringing in the ears, headaches and dizziness. Recently, researchers have achieved these same effects. However, the use of high doses of aspirin is associated with a greater incidence of gastrointestinal bleeding.

The same researchers have established an equally strong link between inflammation, insulin resistance and obesity. Fat cells (adipocytes) are known to produce inflammatory cytokines, proteins that play a key role in inflammation. Consequently, the researchers used a breed of mice with fat cells that produce a high level of inflammatory compounds.  The animals with these fat cells became insulin resistant and developed diabetes. The researchers concluded that they could trigger the development of diabetes simply by inducing inflammation in the animals.

Depression and Alzheimer’s

Scientists now believe that chronic inflammation is involved in the development of major depression that precedes Alzheimer’s disease. Chronic inflammatory changes that are suspected to be a common feature of depression could predispose depressed patients to neurodegenerative changes in later life. In support of this theory, clinical evidence shows that depression commonly precedes Alzheimer’s disease and may be an early manifestation of dementia before cognitive decline becomes apparent. Evidence indicates that chronic low-grade inflammation changes brain structure in a way similar to that seen in Alzheimer’s disease and other dementias. Neuronal loss, for example, is a common feature of major depression and dementia. Scientists have hypothesized that the activation of macrophages in the blood and brain release pro-inflammatory cytokines, which encourages the progress from depression to dementia. Such cytokines stimulate a cascade of inflammatory changes and excessive secretion of cortisol.

Hypertension

C-reactive protein (CRP), a marker of systemic low-grade inflammation, is frequently elevated in essential hypertension. In one study of 36 subjects with essential hypertension, 36 subjects with white coat hypertension (blood pressure that rises only in the doctor’s office), and 36 subjects without hypertension, CRP levels were significantly higher in the essential hypertensive and white-coat hypertensive groups than in the group with normal blood pressure. It was also higher in the essential hypertensive group than in the white-coat hypertensive group.

Joint Health

Inflammation is perhaps best known for its destructive effects on bone and joint health and for the role it plays in arthritis. The cyclooxygenase-2 (COX-2) enzyme is known to produce pro-inflammatory prostaglandins, which ultimately result in the destruction of cartilage.

Cancer

Various forms of cancer are now believed to either have their origin in the inflammatory process or to be worsened by inflammation. In lung cancer, inflammatory signals can promote resistance to apoptosis, the process by which the body rids itself of cancer cells. Inflammation also promotes the multiplication of cancer cells as well as their invasiveness and their ability to spread throughout the body. Inflammation suppresses the immune system and triggers the secretion of factors that enhance angiogenesis, the development of new blood vessels that feed cancer cells. Lung cancer develops in a host environment in which the inflammatory response has become unbalanced, promoting tumor progression. It is thought that inflammation has a similar tumor-promoting effect in other forms of cancer as well.

Extract By Kimberly Pryor
Natural Remedies that can help to reduce Inflammation
Indian Frankincense Gum Extract, also known as Boswellia serrata -  widely used as  a traditional herb in Ayurvedic medicine for treating inflammatory disease and has reported anti-inflammatory and analgesic activity. The resin, or gum, from the plant contains boswellic acids, which produce much of this plant’s anti-inflammatory activity. It is believed that the mechanism of action for the anti-inflammatory activity of the boswellic acids is the ability to inhibit the synthesis of pro-inflammatory leukotrienes and the enzyme 5-lipoxygenase (5-LOX). Several clinical trials have attributed beneficial effects of this herb in treating chronic inflammatory diseases such as rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn’s disease, asthma, and tumor-associated brain edema.

In a randomized, double-blind, placebo-controlled crossover study in 30 patients with osteoarthritis of the knee, Boswellia serrata extract or placebo was given for 8 weeks. All of the patients receiving Boswellia supplementation reported a decrease in knee pain and frequency of swelling, and an increase in knee flexion and walking distance.

Turmeric (Curcuma longa) - is used for numerous inflammatory conditions as it has anti-inflammatory and antioxidant activity. The primary constituent is curcumin, which is believed to exert these anti-inflammatory properties. Preliminary studies have shown turmeric may be supportive in several conditions such as inflammatory bowel disease, rheumatoid arthritis, inflammatory eye diseases, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers.

Curcumin has been shown to inhibit important enzymes that mediate inflammatory processes in the body. These enzymes are cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). Improper up-regulation of COX-2 and iNOS has been associated with the pathology of inflammatory disorders as well as certain types of cancer. A number of studies have been conducted that support curcumin-mediated regulation of the COX and LOX pathways at both the cellular and molecular level.

In one study, the anti-inflammatory properties of turmeric were evaluated using animal models of rheumatoid arthritis. The results showed that turmeric profoundly inhibited joint inflammation and joint destruction in a dose-dependent manner. Turmeric prevented local activation of NFkB, which is involved in regulation of expression of the pro-inflammatory enzymes COX-2 and iNOS. Additionally, inflammatory cell influx, joint levels of pro-inflammatory prostaglandin E2, and local osteoclast (cells that resorb bone) formation were inhibited by turmeric extract treatment.

Bromelain - is the general name for a group of proteolytic enzymes derived from pineapple stems. Through its action on the blood-clotting-related substances fibrinogen and fibrin, bromelain stimulates the production and release of anti-inflammatory prostaglandins (PGs), while simultaneously reducing the production and release of pro-inflammatory PGs.

Ginger root – is called the “universal medicine” in East Indian Ayurvedic medicine. Ginger root contains a veritable cornucopia of natural anti-inflammatory compounds. The USDA Phytochemical Database reported as of 1999 that ginger has more 5-lipoxygenase inhibitors than any other botanical source. Given its balanced anti-COX-2 and anti-5-lipoxygenase activity, ginger root extract provides useful, yet safe anti-inflammatory activity.

Quercetin - reduces the release of histamine, the substance that triggers allergies. Histamine is produced by mast cells. In allergic rhinitis, mast cells in the nasal area increase in number and are thought to play an important role in the nasal symptoms that occur during seasonal allergies. In one study, researchers triggered histamine release in nasal scrapings from seasonal allergy patients exposed to mite antigen. When the nasal scrapings were exposed to quercetin, histamine release was inhibited 46 percent to 96 percent. In another study of rat mast cells exposed to an allergen, quercetin inhibited histamine release by 95 percent and 97 percent.

Fish Oils - provide the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which compete with the omega-6 fatty acid arachidonic acid in inflammatory pathways. Arachidonic acid, commonly ingested from animal products, is the precursor of pro-inflammatory mediators, while EPA and DHA inhibit arachidonic acid metabolism and increase production of anti-inflammatory mediators. These mediators, known as eicosanoids, have opposing activity.

Fish oil supplementation in patients with inflammatory bowel diseases have shown to modulate levels of inflammatory mediators, and may be beneficial for the induction and maintenance of remission in ulcerative colitis.

Researchers have correlated that certain dietary habits such as low intake of fish products, omega-3 PUFAs, and a low omega-3/omega-6 ratio is associated with menstrual pain, which is mediated by inflammatory eicosanoids. One study evaluated the effect of supplementation with omega-3 PUFAs in adolescents with painful menses. The results showed that treatment with fish oil effectively reduced painful menstrual symptoms.

Researchers have investigated omega-3s effects in other inflammatory conditions. One study examined the levels of omega-3s in RBCs to examine the difference between children with atopy (atopic dermatitis, allergic rhinitis, or asthma) and without. Total RBC fatty acid composition showed that total omega-3s were lower, while omega-6 and omega-6/omega-3 ratios were greater in children with atopy compared to controls. In another study, gamma-linolenic acid (GLA) and EPA was supplemented in a group of atopic patients with mild-to-moderate asthma. Asthma questionnaire scores improved and rescue bronchodilator medication use decreased, suggesting that PUFA supplementation can improve patient quality of life and decrease reliance on rescue medication.

In the management of rheumatoid arthritis (RA) and other inflammatory conditions, side effects limit the use of non-steroidal anti-inflammatory drugs (NSAIDs). A clinical trial showed that 39 percent of patients with RA supplemented with cod liver oil were able to reduce their daily NSAID requirement by greater than 30 percent.

Gleditsia sinensis also called Chinese honey locust – was shown in a 2002 study that it possibly inhibit inflammation by reducing the release of histamine from mast cell.* Traditionally, all parts of the Gleditsia sinensis plant have been found to have many beneficial properties.*

Chinese Skullcap – has been used for thousands of years in treating hot and damp conditions, supports digestion and contains bioflavonoids that may enhance liver function. *

Bitter orange – has long history of use as a digestive tonic and is an expectorant and laxative. It is energy enhancing, provides powerful support for circulation and is considered to be one of the strongest chi moving herbs.*

Bai Zhu – in TCM, it is thought to support the functions of the stomach and spleen and its actions also include immune system enhancement, detoxification and support for the function of the adrenal cortex.

Chinese giant hyssop – a warming herb which is used when there is “dampness” within the digestive system, for good appetite and strong digestion.* It is known to benefit blood vessel circulation and used to support vitality.*

References

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  2. Ammon HP. Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases [in German]. Wien Med Wochenschr. 2002;152(15–16):373–378.
  3. Taussig, S. The mechanism of the physiological action of bromelain. Med Hypoth 6 (1980): 99-104.
  4. Funk JL, Frye JB, Oyarzo JN, et al. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006 Nov;54(11):3452-3464.
  5. Hsu CH, Cheng AL. Clinical studies with curcumin. Adv Exp Med Biol. 2007;595:471-480.
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  7. Rao CV. Regulation of COX and LOX by curcumin. Adv Exp Med Biol. 2007;595:213-26.
  8. Kelly G. “Bromelain: A literature review and discussion of its therapeutic applications” Alt Med Rev 1 (1996):243-57.
  9. Haggag EG, Abou-Moustafa MA, Boucher W, Theoharides TC. The effect of a herbal water-extract on histamine release from mast cells and on allergic asthma.J Herb Pharmacother 2003;3(4):41-54.
  10. Srivastava K, Mustafa T. Ginger (Zingiber officinale) and rheumatic disorders. Med Hypoth. 1989;29:25-28.
    Jolad S, et al. Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production. Phytochem. 2004;65:1937-54.
  11. Park K, et al. Inhibitor effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett. 1998;129:139-44.
  12. Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res. 2008 May 26.
  13. Deutch B. Painful menstruation and low intake of n-3 fatty. acids. Ugeskr Laeger. 1996 Jul 15;158(29):4195-8.
  14. Surette ME, Stull D, Lindemann J. The impact of a medical food containing gammalinolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients. Curr Med Res Opin. 2008 Feb;24(2):559-67.

*As per US federal guidelines, we need to inform you that these statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.