the role of anti inflammatory nutrients

8/2/2019 The Role of Anti Inflammatory Nutrients

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Presented By: Ram Chaudhari,

Ph.D., FACN, CNS

Sr. Executive Vice President,

Chief Scientific Officer


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T H E R O L E O F A N T I - I N F L A M M A T O R Y N U T R I E N T S 2 0 1 1

Inflammation is at the Root of Many Diseases

The realization that chronic, low-grade, tissue inflammation is an important factor in thepathogenesis of a variety of chronic diseases has been an important advancement in thescientific understanding of the mechanism by which the disease is caused. Remarkably,inflammation plays an important role in diseases as apparently diverse as cardiovascular

disease, cancer, diabetes, osteoporosis, arthritis, Alzheimers disease, and auto-immunediseases (Figure 1). Moreover, the less dramatic daily discomforts of life, such as chronicpain, depression, memory loss, general cognitive decline, and general muscle fatigue, allseem to be connected in some way to an underlying inflammatory condition. The pharma-ceutical industry has developed a myriad of prescription medications and over-the-counterremedies to treat the symptoms associated with these conditions.

Figure 1. Chronic inflammation is an important risk factor for a variety of chronicdiseases and conditions.

Certain Food Components have Anti-Inflammatory Properties

An important development in nutritional science in recent years has been the discovery ofanti-inflammatory properties of certain nutrients and bioactive food components. There has

also been the rediscovery and increased appreciation of the potential value of certain herbs,spices and other botanical-based traditional medicine approaches that may fight inflamma-tion and help in the prevention or treatment of certain diseases or conditions. This paperwill highlight some of these important anti-inflammatory nutrients and bioactive compo-nents with the intent of increasing awareness of their efficacy and how they may be incor-porated into the development of novel anti-inflammatory fortified-food products.

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Growing Public Awareness of Anti-Inflammatory Benefits of Certain Foods

The general public is less aware of the importance of dietary anti-inflammatory nutrientsthan they should be, but there has been a growing awareness of this concept among themore health-conscious consumer. The latter group has likely gained this awareness fromthe many positive news reports of the health benefits associated with fish consumption and

the role of omega-3 fatty acids, such as DHA (docosahexaenoic acid) and EPA(eicosapentaenoic acid) in reducing inflammation. It is important that this consumer mo-mentum and awareness about anti-inflammatory nutrients is capitalized upon and expandedin the future and that it not be somehow lost among the increasing health concerns associ-ated with mercury and other environmental contaminants found in certain fish species. Theavailability of a variety of novel, consumer-acceptable omega-3 fatty acid-fortified foodproducts, as an alternative to fish consumption, as a source of these important healthy fattyacids will likely be a growth opportunity, as well as the development of other novel anti-inflammatory food products.

The diseases and adverse health conditions mentioned above affect both males and fe-males and are of obvious special concern in older adults, who more likely suffer from, orare increasingly aware of, the issue of chronic disease and disability. In many cases, the

search for anti-inflammatory remedies is driven by an effort to relieve chronic pain, as maybe associated with common conditions such as arthritis.

Anti-Inflammatory Drugs are Big Business

According to the market research company BCC Research, the market for anti-inflammatorydrugs was projected to be $35.5 billion in 2010. Among the diseases associated with theuse of anti-inflammatory medications, the most common are asthma and chronic obstruc-tive pulmonary disease, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseaseand psoriasis (Figure 2).

Figure 2. Diseases associated with the use of anti-inflammatory drugs in 2010.http://www.bccresearch.com/report/PHM048A.html Accessed online July 17,2011.

The older adult group is a clear target for anti-inflammatory remedies. In this regard, froma geographic perspective, certain areas of the world with a very high proportion of elderly,such as Japan, Europe and the United States, may be particularly strong places to engagein anti-inflammation-based marketing strategies for fortified products. Nevertheless, itshould be realized that a strong scientific case can be made that chronic inflammationshould be a concern throughout the life span. For example, there is increasing awarenessin the scientific community that the conditions for chronic disease are actually in many waysset in early development, including during fetal life. This is sometimes referred to as

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metabolic programming or imprinting and is an active area of current research and dis-covery. Thus, in one sense, it is never too early in the life cycle to consider the possiblebenefits of controlling inflammation. It is evident, for example, that inflammation in thepregnant mother can have adverse effects on pregnancy outcome. Likewise, the explosionin childhood obesity in both developed and developing nations is marked by an importantunderlying component of low-grade, chronic inflammation, called metaflammation, that

could set the stage for the development of more adverse health outcomes in the future,such as an increased risk of developing heart disease and type 2 diabetes.

Chronic Pain is an Important Public Health Problem

Important market drivers for anti-inflammatory products include increasing consumerawareness of the connection between good nutrition and health. This includes the notionthat there are specific nutrients and ingredients that have special functional propertiesneeded to improve health and prevent the onset of disease. On an individual level, a sig-nificant segment of society lives with some sort of chronic pain and discomfort, as well asan awareness that the stresses of everyday life may lower immunity and increase suscepti-bility to infections. According to a recently released report from the Institute of Medicine,116 million Americans suffer from chronic pain. This is more people than are affected by

heart disease, diabetes and cancer combined. Thus, pain management is an importantpublic health issue. Pain-associated medical costs in the United States are estimated to be$560-635 billion per year. Since inflammation is often an important component of the pa-thology of pain-producing conditions, the availability of effective anti-inflammatory treat-ments and preventatives is imperative in fighting this condition.

In Demand Anti-Inflammatory Nutrients

There is extensive literature available on thegeneral anti-inflammatory properties of variousnutrients, food-derived components, herbs andvarious botanicals. Moreover, some of thesedietary components have been tested, relatedto the treatment of specific inflammation-baseddiseases. For example, conjugated linoleic acid(CLA) and omega-3 polyunsaturated fatty acidshave been shown to be effective in animalmodels of inflammatory bowel disease, butthere are not strong clinical findings, as yet, tosupport the efficacy of these nutrients in com-bating this condition in patients.1

Much of the available scientific literature is lim-ited to pre-clinical studies in cell culture or ani-mal models. Increasingly, however, the anti-

inflammatory properties of some of these nutri-ents and foods are being identified by examin-ing dietary patterns in epidemiologic studiesand some have been explored more directly in clinical studies. For example, a typical Medi-terranean-style diet that is rich in monounsaturated fatty acids compared to saturated fattyacids, has a high ratio of omega-3-to-omega-6 polyunsaturated fatty acids, with an abun-dance of fruits, vegetables, legumes and grains has an anti-inflammatory effect when com-pared to a typical Western style diet.2 It will be a more difficult, however, to fully elucidatewhich specific components of the Mediterranean diet are responsible for these findings.3

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It also should be noted that there will likely be a strong interaction between a persons ge-netic makeup and their response to specific dietary components. The emerging area ofnutritional genetics (nutrigenomics) and personalized nutrition will likely be a major re-search theme throughout the 21st century as we try to unravel and understand the complexinterplay of various individual genetic alterations and environmental exposures, includingdiet, and specific health risks. An example of this phenomenon that is relevant to our cur-

rent topic is the finding that the apolipoprotein E4 (apoE4) genotype, which is a significantgenetic marker of risk for cardiovascular and Alzheimers disease, is associated with a morepro-inflammatory state, which may be related to the apparent effect of the apoE4 genotypeon the metabolism and retention of vitamin E, an important antioxidant vitamin.4

Moreover, it might be important to consider that the most beneficial aspects of certain die-tary components could be evident only within the context of other dietary constituents orconditions. For example, a recent review of clinical studies5 investigating the role of dietaryfiber on C-reactive protein, an important inflammatory biomarker, found that increased die-

tary fiber consumption reduced C-reactive protein; however, these studies were also associ-ated with weight loss and altered dietary fatty acid composition, which could confoundthese effects. Future clinical studies will need to carefully parse the individual contributionsof dietary fiber on inflammation, as well as the potential combinatorial benefits of various

dietary changes on this condition.

The following sub-sections provide an overview of some peer-reviewed clinical interventiontrials that have studied the anti-inflammatory properties of various nutrients and food fac-tors under a variety of conditions and in healthy and diseased populations. A summary ofthese anti-inflammatory factors is provided in the following Table. More detail concerningthe specific clinical trial can be found in the text below.

Table. Anti-Inflammatory Foods, Nutrients and Bioactive Factors Usedin Clinical Trials

Fruits and Vegetables: Evidence from clinical trials supports a beneficial role of polyphe-nol-rich fruit and vegetable extracts or juices on inflammatory biomarkers. For example, arandomized, control trial of bilberry juice (1 L per day x four weeks) consumption6 com-pared to water (control) in 62 adult male and female Norwegian subjects at risk of cardio-vascular disease indicated a significant salutary effect of bilberry juice on C-reactive protein

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Juices

Bilberry

Orange Tomato

Blackcurrant

Vitamins

Vitamin A

Vitamin C Vitamin D

Vitamin E

Riboflavin

Niacin

Botanicals, Spices

Japanese Knotweed

Curcumin Grape Seed Extract

Minerals

Zinc

Selenium

Manganese

Chromium

Bioactives

Quercetin

EGCG

Soy Isoflavones

eta-Carotene

L-Carnitine CoQ 10

Probiotics

Fatty Acids

DHA

EPA

Arachidonic Acid


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and several other biomarkers of inflammation. Similarly, a Danish study7 investigating theeffects of orange (250 mL per day) and blackcurrant juice (250 mL per day) compared to asugar drink (placebo) on inflammatory markers in 48 patients with peripheral arterial dis-ease observed that following a 28-day treat-ment period there was a significant decrease ininflammatory markers due to the juice treat-

ment. Spanish investigators found that con-sumption of tomato juice containing 21 mglycopene for two weeks resulted in a significantreduction in C-reactive protein, a marker ofinflammation.8 In a clinical trial of 117 healthyadults conducted in the United States, re-searchers found that consumption of encapsu-lated fruit and vegetable juice powder concen-trate for 60 days had a positive effect on vari-

ous inflammatory biomarkers.9 In anotherstudy, researchers in the United Kingdom in-vestigated the effects of grape seed extract, a flavonoid-rich product, as a potential media-tor of inflammation in 32 patients with type 2 diabetes.10 Patients received either GSE (600

mg per day) or placebo for four weeks in a double-blind crossover study. GSE treatmentcaused a significant reduction in inflammation measured by serum C-reactive protein bio-marker. A similar study in healthy pre- and post-menopausal women, conducted in theUnited States, found that consumption of 36 g of lyophilized grape powder for four weekscaused a significant reduction in serum tumor necrosis factor-alpha (TNF-), an importantcytokine that can trigger the inflammatory response.11 Other investigators in the UnitedStates have recently reported that six weeks of treatment with an extract of polygoniumcuspidatum (Japanese Knotweed) that contained 40 mg resveratrol suppressed biomarkersof inflammation in healthy, normal-weight subjects.12

In addition to trials of juices and botanical extracts on inflammation, studies have also in-vestigated the effect mixtures of purified bioactive compounds on inflammation. For exam-ple, Neiman and colleagues13 studied the effect of a bioactive mixture in trained cyclists onexercise-induced inflammation. Forty cyclists were randomized to placebo, quercetin (1000

mg), or a mixture of quercetin plus 120 mg epigallocatechin 3-gallate (EGCG), 400 mg iso-quercetin, and 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fortwo weeks before, during, and one week after three days of heavy exercise exertion. Thebioactive mixture caused a significant reduction in biomarkers of inflammation immediatelyafter the exercise bout.

Curcumin is a traditional Indian spice that has gained much interest as a potential anti-inflammatory compound. A recent clinical study from Japan has investigated whether acombination of soy isoflavones and curcumin could influence the blood levels of prostatespecific antigen (PSA) in men who had elevated PSA, but who did not have evidence ofprostate cancer based on a negative prostate biopsy.14 Eighty-five men were randomized

to receive either placebo or soy isoflavone-curcumin for six months. Changes in PSA, amarker of prostate inflammation, was evaluated before and after supplementation, and theinvestigators found that the mixture significantly reduced serum PSA concentrations. Astudy conducted in India with 72 patients with type 2 diabetes found that 300 mg curcuminfor eight weeks caused a significant reduction in biomarkers of inflammation in the blood.15

Omega-3 fatty acids, such as EPA and DHA, have been shown to have significant anti-inflammatory effects in pre-clinical studies in cell culture, in animal studies and in observa-tional studies in human populations. Surprisingly, however, clinical studies confirming the

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direct beneficial effects of omega-3 fatty acid supplementation on biomarkers of inflamma-tion are generally lacking. Thus, the anti-inflammatory effect of omega-3 fatty acids is con-troversial. However, a recent Swedish study of obese adolescents has provided informationthat omega-3 fatty acid supplementation (1.2 g per day x three months) was associatedwith lower serum biomarkers of inflammation.16

Due to its powerful antioxidant properties, vitamin E has important potential as an anti-inflammatory agent. In a recent study published in the New England Journal of Medicine,investigators studied the effects of vitamin E (800 IU per day x 96 weeks) on non-alcoholicfatty liver inflammation (non-alcoholic steatohepatitis), a common liver disease, in adultswithout diabetes and found that vitamin E treatment was associated with a significantlyhigher rate of improvement in non-alcoholic steatohepatitis compared to placebo and a re-duction in markers of liver inflammation.17 In a small study of 13 older Italian men withimpaired fasting glucose, investigators found that treatment with 1000 IU vitamin E and1000 mg vitamin C for four weeks reduced blood levels of TNF-, an indicator of inflamma-

tion.18 In another study, subjects with metabolic syndrome, which is associated with anincreased risk of diabetes and cardiovascular disease, were randomized to 800 IU per dayof alpha-tocopherol or 800 IU gamma-tocopherol, or a combined vitamin E treatment orplacebo for six weeks. C-reactive protein concentration and serum TNF- was significantly

reduced by the combined treatment and TNF- was also reduced by alpha-tocopherol treat-ment alone.19

Mixtures of antioxidant nutrients have also been investigated for their effects on inflamma-tion in various disease conditions. For example, recently investigators in the United Statesfound that a combination of alpha-tocopherol (800 mg), beta-carotene (24 mg), vitamin C(1000 mg), selenomethionine (0.2 mg), riboflavin (7.2 mg), niacin (80 mg), zinc (60 mg),and manganese (5 mg) consumed daily for four months in patients with a history of spo-radic colorectal adenoma had a beneficial effect on markers of inflammation and oxidativestress.20 Asthma is another inflammatory disease where nutrition may be able to play anameliorating role. A study from Egypt randomly assigned 60 children with asthma to eitherplacebo or a nutrient supplement containing omega-3fatty acids, vitamin C and zinc and found that there wassignificant improvement in pulmonary function tests and

inflammatory markers.21

In a recent study from Iran, 36 patients on hemodialysiswere randomized to receive either placebo or 1000 mgper day L-carnitine for 12 weeks.22 The investigatorsfound that carnitine supplementation was associatedwith a significant reduction in C-reactive protein and thepro-inflammatory cytokine IL-6. A study of zinc supple-mentation in 40 healthy elderly subjects in Detroit foundthat 45 mg zinc per day for six months decreased theconcentration of serum C-reactive protein and various

other inflammatory biomarkers.23

An Iranian study in60 obese prepubescent children found that supplemen-tation with 20 mg zinc for eight weeks was associatedwith a significant decrease in serum C-reactive protein.

Overall, the studies highlighted above represent clinical intervention trials which demon-strate the efficacy of various nutrients and bioactive food factors or botanical sources asanti-inflammatory ingredients.

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Product Applications

A wide variety of delivery vehicles for anti-inflammatory factors in fortified food products ispossible. These include a variety of traditionally fortified foods and dietary supplements. Inaddition, snack foods and beverages should be readily amenable to fortification with anti-inflammatory nutrients and bioactive factors. The wide spectrum of anti-inflammatory in-

gredients highlighted above should provide significant flexibility and many opportunities toincorporate these nutrients and bioactives in many different product types. There will be,of course, specific fortification and formulation challenges that will arise with any specificproduct where professional advice will be helpful.

Fortification and Formulation Challenges

Food and beverage manufacturers worldwide recognize that delivering nutrient value canopen market opportunities and drive sales. Competitive edge can be won through factorsincluding functional ingredient load, health claims and product customization for specificdemographics and health conditions. The key to manufacturers ability to meet the promiseof their nutritional labels and health claims is the stability of the nutrients in their food orbeverage matrix. There are, however, many variables internal and external to the products

environment that affect nutrient integrity, potentially limiting their potency, efficacy andshelf-life. It stands to reason, too, that the affects of these variables are compounded asthe number of functional ingredients being integrated increases.

When designing a food or beverage, it is essential to consider few basic factors as a foun-dation for optimizing nutrient stability:

nutrient activity/bioavailability composition of the finished food manner of addition processing condition and procedures storage and other conditions prior to consumption regulatory status of nutrients purity of ingredients stability and safety aspect of nutrientsPrototypes - Formulations

Beverage (Fruit Flavored/Ready-to-Drink)

Nutrients Per Serving

Vitamin A 2500 IUVitamin E 15 IUVitamin C 60 mgSelenium 70 mcgZinc 3 mgChromium 45 mcgBilberry Extract 10 mgGrape Seed Extract 50 mg

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Vitamin B6 2 mgVitamin B12 6 mcgFolic Acid 200 mcg

Sprinkles (Stick Pack)


Curcumin (Turmeric Extract) 50 mgQuercetin 150 mgCoQ 10 100 mgSoy Isoflavone 100 mgEGCG 50 mgVitamin C 30 mgVitamin E 30 IU

Strawberry Smoothie (Any Fruit Smoothie)


Vitamin A 1000 IUVitamin D 200 IUOmega-3 150 mgResveratrol 50 mgArachidonic Acid 25 mgL-Carnitine 50 mgEGCG 50 mg

Folic Acid 200 mcgVitamin B6 1 mgVitamin B12 3 mcgLycopene 3 mgGlutamine 200 mgVitamin E 30 IU

Vitamin C 30 mgSelenium 70 mcgZinc 3 mgMagnesium 100 mgBilberry Extract 10 mg

Riboflavin 0.5 mgNiacinamide 5 mg

Nutrition Bar


Vitamin A (Beta-Carotene) 2500 IUVitamin D 100 IUVitamin E 30 IUVitamin C 30 mgVitamin B1 0.5 mgVitamin B2 0.7 mgNiacinamide 5 mgCalcium Pantothenate 3 mg

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Vitamin B6 1 mgVitamin B12 3 mcgFolic Acid 200 mcgSelenium 70 mcgZinc 5 mgMagnesium 200 mg

CoQ 10 10 mgOmega-3 100 mg

Future Trends

An important pathologic role of inflammation in many important chronic diseases and condi-tions, such as obesity, is strongly supported by scientific literature. With the predicted ex-

plosion of the elderly population in many countries and the growing obesity epi-demic in both developed and developing countries, there will be a growing mar-ket for products that can deliver efficacious doses of anti-inflammatory nutrientsand bioactive compounds.

Market opportunities may develop in less than traditional areas. For example,

novel food delivery vehicles for anti-inflammatory compounds could be contem-plated that directly provide these anti-inflammatory factors to the site of infectionand inflammation. An example of this application would be in periodontal diseaseor mouth sores where incorporating anti-inflammatory factors in chewing gum,toothpaste, dental adhesives, oral sprays or hard candies could be therapeuticallybeneficial. Additional niche target groups, such as active exercisers, body build-ers and sport players, may find addition of anti-inflammatory factors to energyand sport drinks appealing, while the overweight person on a diet could benefit

by anti-inflammatory compounds in low-cal drinks or in high-fiber bars or otherfoods. Likewise, non-food items, such as topical skin applications or shampoosenriched with natural anti-inflammatory compounds could have some benefit ininflamed skin lesions, such as acne or psoriasis, or for use in sun-protection lo-

tions to reduce the pain and irritation associated with sunburn.

Literature Cited

1. Bassaganya-Riera, J., Hontecillas, R. Dietary conjugated linoleic acid and n-3 polyunsatu-rated fatty acids in inflammatory bowel disease. Current Opinion in Clinical Nutrition &Metabolic Care, 13:569-73.2. Galland, L. Diet and inflammation. Nutrition in Clinical Practice, 25:634-40.3. Calder, P.C., Albers, R., Antoine, J.M., et al. (2009). Inflammatory disease processes andinteractions with nutrition. British Journal of Nutrition, 101 Suppl 1:S1-45.4. Huebbe, P., Lodge, J.K., Rimbach, G. Implications of apolipoprotein E genotype on in-flammation and vitamin E status. Molecular Nutrition & Food Research, 54:623-30.5. North, C.J., Venter, C.S., Jerling, J.C. (2009). The effects of dietary fiber on C-reactive

protein, an inflammation marker predicting cardiovascular disease. European Journal ofClinical Nutrition, 63:921-33.6. Karlsen, A., Paur, I., Bohn, S.K., et al. Bilberry juice modulates plasma concentration ofNF-kappaB related inflammatory markers in subjects at increased risk of CVD. EuropeanJournal of Clinical Nutrition, 49:345-55.7. Dalgard, C., Nielsen, F., Morrow, J.D., et al. (2009). Supplementation with orange and

blackcurrant juice, but not vitamin E, improves inflammatory markers in patients with pe-ripheral arterial disease. British Journal of Nutrition, 101:263-9.

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8. Jacob, K., Periago, M.J., Bohm, V., Berruezo, G.R. (2008). Influence of lycopene and vita-min C from tomato juice on biomarkers of oxidative stress and inflammation. British Journalof Nutrition, 99:137-46.9. Jin, Y., Cui, X., Singh, U.P., et al. Systemic inflammatory load in humans is suppressed byconsumption of two formulations of dried, encapsulated juice concentrate. Molecular Nutri-tion & Food Research, 54:1506-14.

10. Kar, P., Laight, D., Rooprai, H.K., Shaw, K.M., Cummings, M. (2009). Effects of grapeseed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind random-ized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxi-dative stress and insulin sensitivity. Diabetic Medicine, 26:526-31.11. Zern, T.L., Wood, R.J., Greene, C., et al. (2005). Grape polyphenols exert a cardio pro-tective effect in pre- and post-menopausal women by lowering plasma lipids and reducingoxidative stress. Journal of Nutrition, 135:1911-7.12. Ghanim, H., Sia, C.L., Abuaysheh, S., et al. An anti-inflammatory and reactive oxygenspecies suppressive effects of an extract of polygonum cuspidatum containing resveratrol.

The Journal of Clinical Endocrinology & Metabolism, 95:E1-8.13. Nieman, D.C., Henson, D.A., Maxwell, K.R., et al. (2009). Effects of quercetin and EGCGon mitochondrial biogenesis and immunity. Medicine & Science in Sports & Exercise,41:1467-75.

14. Ide, H., Tokiwa, S., Sakamaki, K., et al. Combined inhibitory effects of soy isoflavonesand curcumin on the production of prostate-specific antigen. Prostate, 70:1127-33.15. Usharani, P., Mateen, A.A., Naidu, M.U., Raju, Y.S., Chandra, N. (2008). Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatorymarkers in patients with type 2 diabetes mellitus: a randomized, parallel-group, placebo-controlled, 8-week study. Drugs in R&D, 9:243-50.16. Dangardt, F., Osika, W., Chen, Y., et al. Omega-3 fatty acid supplementation improvesvascular function and reduces inflammation in obese adolescents.Atherosclerosis;212:580-5.17. Sanyal, A.J., Chalasani, N., Kowdley, K.V., et al. Pioglitazone, vitamin E, or placebo fornon-alcoholic steatohepatitis. The New England Journal of Medicine, 362:1675-85.18. Rizzo, M.R., Abbatecola, A.M., Barbieri, M., et al. (2008). Evidence for anti-inflammatoryeffects of combined administration of vitamin E and C in older persons with impaired fastingglucose: impact on insulin action. Journal of the American College of Nutrition, 27:505-11.

19. Devaraj, S., Leonard, S., Traber, M.G., Jialal, I. (2008). Gamma-tocopherol supplemen-tation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stressand inflammation in subjects with metabolic syndrome. Free Radical Biology & Medicine,44:1203-8.20. Hopkins, M.H., Fedirko, V., Jones, D.P., Terry, P.D., Bostick, R.M. Antioxidant micronu-trients and biomarkers of oxidative stress and inflammation in colorectal adenoma patients:results from a randomized, controlled clinical trial. Cancer Epidemiology, Biomarkers & Pre-vention, 19:850-8.21. Biltagi, M.A., Baset, A.A., Bassiouny, M., Kasrawi, M.A., Attia, M. (2009). Omega-3 fattyacids, vitamin C and Zn supplementation in asthmatic children: a randomized self-controlledstudy.Acta Paediatrica, 98:737-42.

22. Shakeri, A., Tabibi, H., Hedayati, M. Effects of L-carnitine supplement on serum inflam-matory cytokines, C-reactive protein, lipoprotein (a), and oxidative stress in hemodialysispatients with Lp (a) hyperlipoproteinemia. Hemodialysis International, 14:498-504.23. Bao, B., Prasad, A.S., Beck, F.W., et al. Zinc decreases C-reactive protein, lipid peroxi-dation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as anatheroprotective agent. The American Journal of Clinical Nutrition, 91:1634-41.

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