Inflammation in Asthma

(Some of this material adapted from Joseph Pizzorno, Total Wellness.)

Inflammation is a normal and necessary body function. Through inflammation, the body removes damaged cells , eliminates toxins, fights invading organisms and begins the repair process. When inflammatory processes are out of balance, not only are abnormal cells and toxins removed but healthy tissues are also damaged and, in some instances, a self perpetuating, progressively destructive inflammatory process can ensue.

This imbalance can present in three different forms—excessive activation of the inflammatory process (hypersensitivity); excessive inflammatory response to damage or provocation (overreaction) and inadequate quenching of the inflammatory process when the job is done.

If damage to a cell is slight, a special organ (an organelle) within the cell—the lysosome—ruptures, releasing enzymes which begin to digest damaged parts of the cell. If damage is small, cell is then rpaired and normal function is restored. When damage is severe, the entire cell is digested and a new cell regenerated. When many cells are involved, a much more extensive process begins, releasing two classes of chemicals into surrounding tissues:

(1) vasoactive mediators—histamine, leukotrienes, prostaglandins, serotonin, bradykinin—which cause local blood vessels to dilate and cipillaries become more permeable. More blood and greater permeablity allows better access for white blood cells and needed nutrients and

(2) chemotactic factors—lymphokines, monokines, leukotrienes, prostaglandins— attract white cells to the region and stimulate them to digest damaged tisues (phagocytosis). White cells also release powerful oxidizing agents to destroy any pathogens. The pathogens release their own chemicals also. If this inflammatory process is not limited, then surrounding healthy tissue can itself be damaged.

Healthy tissues release anti-inflammatory prostaglandins, antioxidants to neutralize inflammatory chemicals, anti-chemotactic chemicals to the white cells to stop their action; and proteolytic enzymes to break down the digestive enzymes released by the white cells.

When the inflammation process is finished, the repair process begins; and the body regenerates new tissue. If the inflammatory process does not stop, ensuing chronic inflammation is a central feature of a number of immune system disorders.

ESSENTIAL FATTY ACIDS

Inflammatory activity is determined by a number of factors. One is the ratio of pro-inflammatory to anti inflammatory eicosanoids (tiny but powerful hormone-like substances involved in the regulation of many basic body functions) in the cell membranes, the fatty film that surrounds most cells. The ratio of these substances is determined by (among other things) dietetic consumption of essential fatty acids (EFAs), and by the efficiency of different enzymes needed to convert these EFAs into different eicosanoids.

The two essential fatty acids are linoleic acid (LA—the orignal "parent" of the omega 6 line of fatty acids), which is very common in human diets today and alpha linolenic acid (ALA—the parent of the omega 3 line) which is much less common, perhaps by a ratio of 1 to 10 or 1 to 20 in the typical diet today. Arachidonic acid (AA), a longer chain metabolite of LA is the precursor of most inflammatory eicosanoids, yet the human body needs some AA, particularly in the brain Some experts believe that most arachidonic acid in our bodies is of dietary origin, coming from land animal products, meat, eggs and dairy but this is not universally accepted. The body can make AA from LA.

Fatty acids of the omega 3 line originate in vegetables but in very small quantities apart from a few plants such as flax. They can also be found in the diet in fish and marine products in longer chain, more evolved form, notably eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), precursors of anti-inflammatory eicosanoids.

[The following is a hodgepodge of pertinent studies and comments which will suffice until an improved version appears.]

IMBALANCES and INCREASED INFLAMMATION

Many steps in the conversion of fatty acids to pro- or anti-inflammatory eicosanoids use the same enzymes. This means that there is competition: an excess of one fatty acid tends to hog an enzyme system, resulting in decreased conversion of fatty acids. Conversely, a deficiency of one fatty acid will result in excessive conversion of the others. (Siguel, E.N., Maclure, M: Relative enzyme activity of unsaturated fatty acid metabolic pathways in humans. Metabolism 36:664-69, 1987)

Higher intake of animal fats correlates directly with levels of arachidonic acid and inflammatory mediators in the cell membranes and blood. (Whelan, J, et al: Dietary arachidonate enhances tissue arachidonate levels and eicosanoid production in Syrian hamsters. JNutr 123:2174-85, 1993)

Conversely a diet high in fish, flax seeds or borage seed oils results in substantially less arachidonic acid in cell membranes, lower levels of inflammatory chemicals and higher levels of anti-inflammatory chemicals. (Fat: If you can't bear to pare it. Science news 149:108, 1996) Alcohol consumption inhibits the production of anti-inflammatory eicosanoids (no footnote but believable).

The past century has seen a dramatic increase in the consumption of arachidonic acid (from animal products) and transfatty acids (found in hydrogenated oils): a decrease in certain types of essential fatty acids (from fish, nuts and seeds), and the oxidation, transformation and destruction of EFAs from processing and cooking. This has led to an imbalance of EFAs in the blood and cell membranes of at least 10% of the US populace (Siguel, EN: Essential Fatty Acids in Health and Disease. Nutrek Press, Brookline, MA 1994) Trans fatty acids have their hydrogen atoms on both sides of the molecule, which the body recognizes as saturated fat. These interfere with the production of the anti-inflammatory series 3 group of prostaglandins by inhibiting the delta 6 desaturase enzyme. (Trans Fatty Acids: The new enemy. Harvard Heart Letter 4: 1-3, 1994)

Some humans are deficient in enzymes required to convert EFAs to anti-inflammatory eicosanoids, due to genetic tendency, environmental toxins, diet, age, disease, or a deficiency of vitamins and minerals needed to activate the enzymes necessary. People with atopic (allergic) eczema have a deficient D6D enzyme pathway. Zinc supplements help to strengthen this process ( Manku, M. Horrobin, D et al: Reduced levels of prostaglandin precursors in the blood of atopic patients: Defective delta-6-desaturase function as a basis for atopy. Prostaglandins, Leukotrienes and Medicine 9:615-28, 1982.

Patients with eczema have lower levels of d6d required for converting fatty acids to counter inflammatory prostaglandins. Infants with lower levels of DGLA in the blood have a greater risk of developing eczema as children (Galli, E et al: Analysis of polyunsaturated fatty acids in newborn sera: a screening tool for atopic disease? Br J Dermatol 130: 752-56, 1994) Supplementation with EPA from various sources improves conditon of eczema patients though effects take several months to develop. (Kerscher, MJ and Korting, HC: Treatment of atopic eczema with evening primrose oil: Rational and clinical results. Clin Investig 70: 167-71, 1992) (Fish again for dinner! The role of fish and other dietary oils in the therapy of skin disease. J Am Acad Dermatol 19: 1073-80, 1988).

Excessive Inflammatory Stimulation

Certain drugs, foods, food additives and environmental toxins increase the activity of the inflamatory process. Due to an enzyme defect, about 10% of asthmatics have severe reactions to sulfite (Tarlo, SM and Sussman, GL: Asthma and anaphylactoid reactions to food additives. Can Fam Phys 39:1119-23, 1993). Coloring agents, flavorings, preservatives and emulsifiers have been shown o cause inflammatory problems in asthma and eczema. Yellow dyes from tartrazine are especially problematic (Smith, JM: Adverse reaction to food and drug additives. Eur J Clin Nutr 45: 17-21, 1991)

AntiInflammatory Substances in Diet

Antioxidants such as vitamins C and E inhibit the synthesis of proinflammatory eicosanoids and help quench the inflammatory process. Several bioflavonoids stabilize cells that secrete inflamatory chemicals. Cells with adequate amounts of antioxidants in their membranes are better able to protect themselves from the damaging oxidizing chemicals released during the inflammatory process.

Carotenoids are the most widespread group of naturally occurring pigments (ie color; flavonoids perform similar important functions), and have potent antioxidant properties, protecting the body from free radicals and the body's own inflammatory process (Burton, G and Ingold, K: Beta-carotene: an unusual type of antioxidant. Science 224: 569-73, 1984)

Flavonoids stabilize the membranes of of inflammatory cells, limiting their secretion of histamine and other chemicals, increasing intracellular vitamin C levels , decreasing capillary permeability and neutralizing free radicals. Cody, V, Middleton, E and Harborne, JB: Plant flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure Activity Relationships. Alan R. Liss, New York, 1986).

Certain carotenoids concentrate in specific tissues, for example the carotenoid lutein (found in spinach) concentrate in the macula of the eye, the part responsible for acute vision. (Bunce, GE: Nutrition and eye disease of the elderly. J Nutr Biochem 5:66-76, 1994). The flavonoid anthocyanidins concentrate in the collagen, where they inhibit its destruction. Collagen is destroyed in inflammatory conditions involving joints and cartilege.

DIETARY STRATEGIES to COUNTER INFLAMMATION

Normalize inflammatory eicosanoids; optimize levels of anti-inflammatory nutrients, avoid chemicals and substances that overstimulate pro-inflammatory pathways.

Vegetarian diets are often beneficial probably due to an decrease in dietary arachidonic acid, and an increase in other EFAs and dietary antioxidants. (Lucas, P and Power, L: Dietary fat aggravates rheumatoid arthritis. Clinical Research 29:754A, 1981) (Lindahl, O, Lindwall, L et al: Vegan diet regime with reduced medication in the treatment of Bronchial Asthma. J Asthma 22:45-55, 1985) However diet alone takes a long time to correct this imbalance since not only are the fatty acids in blood and cell

membranes out of balance but most of the 20 to 50 pounds of stored body fats will also contain this imbalance. (Lee, TH and Arm, JP: Prospects for modifying the allergic response by fish oil diet. Clin Al 16:89-100, 1986) Fish oil supplementation improved respiratory function after 9-12 months. (Dry, J and Vincent, D: Effect of fish oil diet on asthma. Int ArchAllImmunol 95:156-7, 1991) Garlic and onions in the diet may have beneficial influences on asthma and allergy. (Vanderhoek, J et al: Inhibition of fatty acid lipooxygenase by onion and garlic oils. Biochem Pharmac 29:3169-73, 1980) (also Prevention of allergen induced bronchial constriciton in sensitized guinea pigs by crude alcohol onion extract. Agents Action 14:626-30, 1984

Omega 3 and fish oils are beneficial in inflammatory disease (Knapp, HR: Omega 3 fatty acids in respiratory disease. J Am Col Nutr 14: 18-23, 1995)(Berth-Jones, J et al, Evening primrose oil and atopic eczema Lancet, 345:520, 1995) Eicosapentanoic acid inhibits inflammatory response by inhibiting the release of arachidonic acid from cell membranes; decreases leukotriene synthesis and forms less potent inflammatory eicosanoids. (Lee, T, Hoover, R et al Effect of dietary enrichment with EPA and DHA on in vitro neutrophil and monocyte leukotriene generation and neutrophil generation. NEJM 312: 1217-24, 1985) (Strasser, T, Fischer, S and Weber, P: Leukotriene B5 is formed in human neutrophils after dietary supplementation with EPA. Proc Nat Acad Sci 82:1540-3, 1985) EPA competes with arachidonic acid for the same enzymes AA uses to produce inflammatory eicosanoids.

The addition of gamma linolenic acid from evening primrose oil has been shown to lead to the reversing of neurological damage in diabetics by bypassing the d6d enzyme. (Horrobin, DF, Review article: Medicinal uses of essential fatty acids, Vet Dermatol 4:161-66, 1993)

In a study of patients with ulcerative colitis, simple supplementation with fish oils resulted in a 65% decrease in levels of inflammatory leukotrienes and a 75% decrease in their clinical systems. (Stenson, WF et al: Dietary Supplementation with fish oil in ulcerative colitis. Ann Int Med 11:609-14, 1992)

Quenching Inflammatory Reactions

Since the inflammatory process is necessary to fight infection, it may be counterproductive to use antiinflammatory supplements in excess. Vit C is a water soluble nutrient with powerful antihistaminic effects (Levine, M New concepts in the biology and biochemistry of ascorbic acid. NEJM 314:892-902, 1986) (Johnston, CS et al: Antihistamine efects and complications of supplemental vitamin C. J AM Diet Assoc 92:988-89, 1992)

Vit E quenches many types of free radicals and inhibits production of proinflamatory eicosanoids from arachidonic acid. (Panganamala, RV and Cornwell, DG: The effects of vitamin E on arachidonic acid metabolism. AnnNYAcda of Sci 393:376-91, 1982)

Quercetin (a flavonoid found in high quantities in onions) stabilizes cell membranes, calms activated neutrophils, neytralizes inflammatory chemicals an inhibits the release of histamine. (Middleton, E and Drzewieki, G: Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol 33:3333-38, 1984) (Busse, WW, Kopp, DE and Middleton, E: Flavonoid modulation of human neutrophil function. J llergy Clin Immun 73:801-9, 1984) Quercetin also has been shown to inhibit many steps in the production of proinflammatory prostaglandins and leukotrienes. [he recommends 500mg per day] (Yashimoto, T et al: Flavonoids: potent inhibitors of arachidonate 5-lipooxygenase. Biochem Biophys Res Common 116:612-18, 19830 (Ford-Hutchinson, AW: Leukotriene involvement in pathological processes. J Allergy Clin Immunology 74:437-40, 1984)

Selenium appears to reduce inflammation by stimulating the activity of glutathione peroxidase (an enzyme that neutralizes free radicals), improving phagocytic activity of white blood cells and decreasing the production of pro inflammatory prostaglandins. Levels of selenium dependent enzyme glutathione peroxidase found to be significantly lower in asthmatics than in healthy individuals. (Flatt, A et al. Reduced selenium in asthmatic subjects in New England. Thorax, 1990; 45: 95-99) Asthmatic subjects improved by dietary selenium supplementation. (Hasselmark, L, et al. Selenium supplementation in intrinsic asthma. Allergy, 1993; 48: 30-36) Selenium is necessary for optimal functioning of the immune system. (Kiremidjian-Schumacher, L; Stotzky, G. Selenium and immune responses. Environ Res, 1987; 42: 277-303) (Peretz, A et al. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium enriched yeast. Am J Clin Nutr, 1991;51:1323-1328) (Arvilommi, H, et al. Selenium and immune functions in humans. Infect Immun, 1983; 41: 185-189) Typical US diet contains 70-100 mcg of selenium, some Americans get less than 50 mcg. (Welsh, SO. Selenium in self selected diets of Maryland residents. JAm Diet Assoc, 1981; 79: 277-285)