Controlling Inflammation in the GI Tract and Throughout the Body

By Chris D. Meletis, ND

Unchecked inflammation is one of the foremost causes of premature aging and countless devastating health conditions. The inflammatory process is associated with an overwhelming and crippling effect on the overburdened health care system of North America, including coronary artery disease, major depression, and cancer. Furthermore, diseases such as arthritis, Crohn’s disease, ulcerative colitis, and systemic lupus erythematosus all possess major inflammatory components that contribute to the suffering and progression of the disease process.

The GI tract plays a pivotal role controlling inflammation and serves as the interface between the “macro-external” world and the well-ordered “microinternal” world of the 75 trillion cells that compose the human frame. The GI tract controls nutrient absorption from the intestinal lumen to the systemic circulation and protects against invasion from microbes and other antigens by inducing an immune response that further contributes to the inflammatory cascade. Loss of GI integrity leads to increased local inflammation in the gut, which triggers increased intestinal permeability. This allows more dietary antigens access to the systemic circulation, which can lead to the development of food allergen reactivity and the propagation of systemic immune and inflammatory reactivity.1

Altered intestinal permeability results in increased food antigen access to the systemic circulation, predisposing other organs and systems of the body to allergic reactions and inflammation.2

Each meal consumed challenges the GI tract with the demands of digestion, selective absorption of key nutrients and food allergens. When seeking to shift the body’s ecology, it is imperative to alter the global cellular burden, liberating energy and function towards balance and away from the disharmony arising from the barrage of the external entropy that the body must defend against constantly.

Clinically, the delivery of key antiinflammatory nutrients and botanicals in a hypoallergenic, protein-rich, low-sodium, powdered drink allows the busy clinician to directly support the GI lumen with scientifically validated nutraceuticals that fortify intestinal integrity and lessen local tissue and systemic cellular inflammation. The following discussion highlights key nutrients required within the GI tract and for overall cellular demands throughout the body to regain and sustain healthful ecology and physiology.

Vitamin B6

Low vitamin B6 (pyridoxine) levels play several roles in the etiology and pathogenesis of chronic inflammation and inflammatory diseases. Pyridoxinedeficient rats developed increased concentrations of thiobarbituric acid reactive substances (indicators of lipid peroxidation) by up to 30-43 percent, suggesting an enhanced inflammation response caused by pyridoxine deficiency.3

Another study demonstrated that median pyridoxine levels were significantly lower in humans with inflammatory bowel disease (IBD) compared to controls and were even lower in patients with active IBD compared to those whose disease was quiescent. In addition, lower pyridoxine levels were positively correlated with CRP serum levels, and hyperhomocysteinemia occurred more frequently in patients with lower pyridoxine levels.4 Decreased levels of plasma pyridoxal-5-phosphate, the active form of vitamin B6, were associated with higher levels of CRP independent of total plasma homocysteine. The researchers hypothesized that such evidence may indicate that vitamin B6 deficiency contributes to chronic inflammatory processes.5 Another aspect of inflammation in which vitamin B6 is involved is fatty-acid metabolism. Inhibition of delta-6-desaturase (D6D), which is both the initial and rate-limiting enzyme in suboptimal levels of vitamin B6, are associated with increased risk for cardiovascular disease and rheumatoid arthritis.

Vitamin E, Magnesium and Zinc

Additional key nutritional factors involved in positive up-regulation of D6D include vitamin E, magnesium and zinc.6 The enzymatic activity of D6D was increased to twice that of baseline level in subjects when their vitamin E microsomal membrane concentrations were increased, reflecting the vitamin’s role in controlling the membranous metabolism of PUFAs.7 In addition, zinc assists in converting LA to GLA via D6D, and zinc deficiency produced an EFA deficiency and downregulation of D6D. Magnesium deficiency contributed to decreased formation of D6D molecules, resulting in a less-rapid conversion of LA to GLA in liver microsomes.8By supplying patients with proper nutritional doses of these enzymatic cofactors, efficient activation of this D6D can induce complete fatty acid metabolism and production of noninflammatory fatty-acid products, helping to further reduce chronic inflammatory patterns.

Boswellia

Boswellia serrata is used widely as a traditional herb in Ayurvedic medicine. The resin, or gum, from the plant contains pentacyclic triterpenes (boswellic acids), which produce much of this plant’s antiinflammatory activity. The acids contained in boswellia inhibit the enzyme 5-lipoxygenase by binding to the enzyme, resulting in decreased LT production in neutrophilic granulocytes. Several clinical trials have attributed beneficial effects of this herb in chronic inflammatory diseases, such as rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn’s disease, asthma, and tumor-associated brain edema.9

In patients with colitis, a gum resin extract of Boswellia serrata was supplied at a dose of 900 mg, three times per day, for six weeks while a control group was maintained on 3 grams per day of sulfasalazine for six weeks. Ninety percent of the boswellia-treated patients experienced improvements in stool properties, histopathology, and levels of hemoglobin, iron, calcium, phosphorus, proteins, and total leukocytes and eosinophils, with few side effects, while 60 percent of the sulfasalazine-treated patients experienced similar results. However, 14 of the 20 boswelliatreated patients experienced remissions, while only 4 of the 10 sulfasalazine-treated patients reached remission.10

Boswellia has been proven to support the health of asthma patients also, and the beneficial effects are attributed to LT inhibition. Seventy percent of subjects who were treated with 300 mg of the herb, three times per day, for six weeks, experienced improvements in forced expiratory volume 1 (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR). Moreover, these same subjects had decreased eosinophilic counts and erythrocyte sedimentation rates, plus subjective improvements. The placebo group experienced a 27 percent improvement overall.11

Stephania tetrandra

Stephania tetrandra is an herb traditionally used for its anti-inflammatory, antioxidant, immune modulating, antifibrogenic, and anti-allergy activity. Its main anti-inflammatory constituents are tetrandrine and fangchinoline. Studies show that the constituent tetrandrine suppressed the lipopolysaccharide (LPS) induction of nitric oxide (NO) release and prostaglandin E2 (PGE2) generation. It also significantly attenuated the LPS-induced transcription of the pro-inflammatory cytokines TNF-a, IL-4 and IL-8 and significantly blocked the LPS induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression.12

Research has also alluded that tetrandine inhibits IL-1 and TNF-a release from monocytes, and inhibits intercellular adhesion molecule-1 (ICAM-1) expression, which may indicate a mechanism by which it exerts its anti-inflammatory activity.13 Tetrandine has been shown to be particularly beneficial in rheumatic conditions such as rheumatoid arthritis, which is believed to be due to inhibition of lymphocyte proliferation and inhibition of cyclooxygenase-1 (COX-1) activity.14 Tetrandine also works synergistically with chemotherapy to induce apoptosis in cancer cell lines.15

Holy Basil (Ocimum sanctum)

Holy basil (Ocimum sanctum) has numerous traditional uses including antiinflammatory, antimicrobial, anticancer, and analgesic action. Holy basil blocks both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, which may be responsible for the antiinflammatory activity.16 Studies also have shown that holy basil inhibits both COX-1 and COX-2 pathways. In fact, the constituent eugenol demonstrated 97 percent cyclooxygenase-1 inhibitory activity.17

Ginger (Zingiber officinalis)

Ginger root (Zingiber officinalis) has historically been used for its anti-inflammatory antipyretic, analgesic, sedative, and antibiotic activity. Ginger contains several active constituents such as gingerol, gingerdione, and shogaol. Evidence shows that ginger extract significantly inhibited the activation of TNF-alpha and COX-2 expression in human synoviocytes with suppression of NF-kappaB and IkappaBalpha induction as well as suppressed the production of TNF-a and PGE2.18 In addition, ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase.19 One study examined the effects of ginger supplementation on musculoskeletal pain and arthritis. Results showed that more than three-quarters of both osteoarthritis and rheumatoid arthritis patients experienced, to varying degrees, relief in pain and swelling, and all of the patients with muscular discomfort experienced relief in pain.20

Green Tea (Camellia sinensis)

Green tea is a widely used botanical studied for its anti-inflammatory, anticancer, and antioxidant activity. Many of the benefits are attributed to the catechins epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC). Animal models show that green tea inhibits the production of leukotriene B4 and 5-lipooxygenase activity.21 Also, a study demonstrated that human chondrocytes pretreated with EGCG showed a dose-dependent inhibition in the production of NO by 48 percent and PGE2 by 24 percent, which correlated with the inhibition of iNOS and COX-2 activity. In addition, IL-1 beta-induced expression of iNOS and COX-2 was also markedly inhibited in human chondrocytes pretreated with EGCG. EGCG also inhibited the IL-1 beta-induced LDH release in chondrocytes cultures.22 Another study found that EGCG inhibits TNF-a-mediated activation of the NF-kappaB pathway, with inhibition of IL-8 gene expression.23

New Anti-Inflammatory Drink

Advanced Inflammation Control Powder is a new low-sodium, anti-inflammatory drink mix that combines the nutrients and botanicals discussed above with other potent anti-inflammatory herbs including turmeric, D-limonene, luteolin and rosemary. It also contains rice protein, making it a highly nutritious, hypoallergenic drink suitable for most patients. When combined with a low-inflammation diet, it can serve as a proactive way for patients to inhibit inflammation that may be brewing under the surface as well as to stop inflammatory states involved in a variety of chronic health concerns.

References

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2. Buckley RH, Metcalfe D. Food allergy. JAMA. 1982;248:2627–2631.

3. Lakshmi R, Lakshmi AV, Divan PV, Bamji MS. Effect of riboflavin or pyridoxine deficiency on inflammatory

4. Saibeni S, Cattaneo M, Vecchi M, Zighetti ML, Lecchi A, Lombardi R, Meucci G, Spina L, de Franchis R. Low vitamin B6 plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: Role of inflammation and correlation with acute phase reactants. Am J Gastroenterol. 2003;98:112–117.

5. Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J. Low circulating vitamin B6 is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation. 2001;12;103:2788–2791.

6. Despret S, Dinh L, Clement M, Bourre JM. Alteration of delta-6 desaturase by vitamin E in rat brain and liver. Neurosci Lett. 1992;145:19–22.

7. Ayala S, Brenner RR. Essential fatty acid status in zinc deficiency: Effect on lipid and fatty acid composition, desaturation activity and structure of microsomal membranes of rat liver and testes. Acta Physiol Lat Am. 1983;33:193–204.

8. Mahfouz MM, Kummerow FA. Effect of magnesium deficiency on delta 6 desaturase activity and fatty acid composition of rat liver microsomes. Lipids. 1989;24:727–732.

9. 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.

10. Gupta I, Parihar A, Malhotra P, Gupta S, Ludtke R, Safayhi H, Ammon HP. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med. 2001;67:391–395

11. Gupta I, Gupta V, Parihar A, Gupta S, Ludtke R, Safayhi H, Ammon HP. Effects of Boswellia serrata gum resin in patients with bronchial asthma: Results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res. 1998;3:511–514.

12. Wu SJ, Ng LT. Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in human monocytic cells. Biol Pharm Bull. 2007 Jan;30(1):59–62.

13. Chang DM, Kuo SY, Lai JH, Chang ML. Effects of anti-rheumatic herbal medicines on cellular adhesion molecules. Ann Rheum Dis. 1999 Jun;58(6):366–371.

14. Long Q, Qiu J. [Effects of ethanol extracts from Triptergium wilfordii hook and Stephania tetrandra S. Moore on lymphocytes and cyclooxygenase]. Zhong Yao Cai. 2004 Nov;27(11):851–853.

15. Wei J, Liu B, Wang L, Qian X, Ding Y, Yu L. Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines. Cancer Chemother Pharmacol. 2007 Oct;60(5):703–711. Epub 2007 Jan 26.

16. Singh S. Comparative evaluation of antiinflammatory potential of fixed oil of different species of Ocimum and its possible mechanism of action. Indian J Exp Biol. 1998 Oct;36(10):1028–1031.

17. Kelm MA, Nair MG, Strasburg GM, DeWitt DL. Antioxidant and cyclooxygenase inhibitory phenolic compounds from Ocimum sanctum Linn. Phytomedicine. 2000 Mar;7(1):7–13.

18. Frondoza CG, Sohrabi A, Polotsky A, Phan PV, Hungerford DS, Lindmark L. An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures. In Vitro Cell Dev Biol Anim. 2004 Mar–Apr;40(3– 4):95–101.

19. Grzanna R, Lindmark L, Frondoza CG. Ginger—an herbal medicinal product with broad anti-inflammatory actions. J Med Food. 2005 Summer;8(2):125–132.

20. Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypotheses. 1992 Dec;39(4):342–348.

21. Choi JH, Chai YM, Joo GJ, Rhee IK, Lee IS, Kim KR, Choi MS, Rhee SJ. Effects of green tea catechin on polymorphonuclear leukocyte 50-lipoxygenase activity, leukotriene B4 synthesis, and renal damage in diabetic rats. Ann Nutr Metab. 2004;48(3):151–155. Epub 2004 May 6.

22. Ahmed S, Rahman A, Hasnain A, Lalonde M, Goldberg VM, Haqqi TM. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic Biol Med. 2002 Oct 15;33(8):1097–1105.

23. Wheeler DS, Catravas JD, Odoms K, Denenberg A, Malhotra V, Wong HR. Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr. 2004 May;134(5):1039–1044.

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