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Scientific Information For Doctors
Research Evidence
The majority of this website is written for laypeople who wish to understand the relationship between inflammation and chronic disease. However, this section contains information for doctors, which is condensed into short paragraphs and tables for easy access. The citations can be found at the end of this page. The Deflaming Guidelines and the associated MP3 Audio Presentation are based on the citations in this section.
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Important Anti-inflammatory Educational Information
"Deflaming" is the term we coined to describe the process of inflammation reduction. We can deflame with both diet and supplements.
Click here for the Deflaming Guidelines, which will open as a PDF document that you can print. The Deflaming Guidelines provide the important details about how to reduce inflammation (deflame) with diet and nutritional supplements.
We also have an MP3 audio version of the Deflaming Guidelines available.
Part 1 describes deflaming with diet.
Part 2 describes deflaming with nutritional supplements.
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Whether you are a medical doctor, osteopath, chiropractor, podiatrist, or physical therapist, we now know that the majority of conditions we treat are caused to varying degrees by inflammation. And during the past 20 years, the evidence clearly indicates that dietary factors function to promote or reduce the ongoing inflammatory potential within the body. Despite this fact regarding disease causation, much of our training focuses on the passive care we are to provide patients, and little time is spent on developing a deep understanding of the relationship among nutrition, chronic inflammation, and disease expression, or the manner in which we should clinically apply nutrition in our respective practices.
In short, our nutritional applications should be similar in most clinical encounters. We should recommend that patients adhere to an anti-inflammatory diet. That is, our patients are currently “inflamed” and need to be “deflamed.”
Below you will see 3 tables that outline the inflaming and deflaming factors related to nutrition. Each provides a different vantage point to view important nutritional inflaming/deflaming issues. You will notice that tables 1-3 are complementary and consistent.
Table 1 - The majority of information contained in table one comes from an excellent paper by Cordain et al. (1). The authors indicate that 72.1% of our calories come from dairy products, cereals, refined sugars, refined vegetable oils, and alcohol. We eat fatty domestic meats [i.e., obese meat] versus lean. We typically eat omega-6 eggs versus omega-3. And we eat maybe 5-10% of calories from fruits and vegetables. Table 1 lists 7 key dietary imbalances created by our modern pro-inflammatory diet and the associated diseases.
Table 2- Lists the nutritional drivers of inflammation and the pro-inflammatory biochemical changes that occur.
Table 3 - Lists several of the known inflammatory factors and their nutritional modulation.
Table 1. Dietary imbalances and the diseases they promote.
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Dietary Imbalances
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Diet-driven Diseases
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1) High glycemic load foods (high sugar, excessive grain consumption), lead to insulin resistance (1).
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1a) Diseases of insulin resistance include: obesity, coronary heart disease (CHD), type 2 diabetes, hypertension, and dyslipidemia [elevated serum triacylglycerols, small-dense, LDL cholesterol and reduced HDL cholesterol], myopia, acne, gout, polycystic ovary syndrome, epithelial cell cancers (breast, colon, and prostate), male vertex balding, skin tags and acanthosis nigricans (1).
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2) Fatty acid composition (high n-6 fatty acids, low omega-3, excessive saturated fat intake, trans fatty acids (1) [trans fats are listed below in Table 2]
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2a) Increased n-6 consumption has been associated with several diseases: heart attack, thrombotic stroke, arthritis, asthma, colitis, headaches, menstrual cramps, osteoporosis, cancer, endometriosis, Alzheimer’s disease, vascular dementia, diabetes, hypertension, multiple sclerosis, depression (2-8,31).
2b) Excessive saturated fat from obese animal fat (standard feedlot meat that most eat) is a driver of hypercholesterolemia and heart disease (1).
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3) Macronutrient composition (1). The imbalance discussed here is the excessive consumption of refined carbohydrates, cereal grains, flour products, and fatty foods (fat modern meat and fatty acid imbalances), and is outlined above in #s1-2.
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4) Low micronutrient density in modern diet due to increased comsumption of refined foods (1). Magnesium and vitamin D are examples of well-studied nutrients in relation to chronic disease.
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4a) Magnesium deficiency/insufficiency is linked to several conditions: headaches, sudden death, accelerated atherosclerosis, cardiovascular disease, hypertension, stroke, renal tubular disorders, osteoporosis, diabetes mellitus, asthma, preeclampsia & eclampsia, and neurologic & psychiatric conditions (9).
4b) Vitamin D deficiency/insufficiency is linked to several conditions: low back pain, musculoskeletal pain, osteoporosis, osteoarthritis, type 2 diabetes, hypertension, CV disease, syndrome X, multiple sclerosis, PCOS, depression, epilepsy, prevention of cancer, prevention of type 1 diabetes (10).
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5) Acid-base balance. Meat, fish, chicken, and eggs are acidic foods and should be consumed, and they should be buffered by alkaline fruits and vegetables. Instead, today we replaced fruits and vegetables with acidic grains and cheese (1).
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5a) Outcome of increased tissue acidity include: osteoporosis, age-related muscle wasting, calcium kidney stones, hypertension, exercise-induced asthma, slow the progression of age- and disease-related chronic renal insufficiency (1). Chronic pain is also a possibility, as a low pH drives nociception and pain (11,12).
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6) Sodium-potassium ratio (1). Today we consume about 75% less potassium than we need,
**Your patients should NOT supplement with potassium. Potassium must be consumed in food, and best source are fruits and vegetables, particularly leafy greens.
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6a) Outcome of altered sodium/potassium balance: hypertension, stroke, kidney stones, osteoporosis, gastrointestinal tract cancers, asthma, exercise-induced asthma, insomnia, air sickness, high-altitude sickness, and Meniere’s Syndrome (ear ringing) (1).
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7) Fiber content of the modern diet is terribly low (about 15 grams per day). Standard recommendation is about 25-30 grams per day (1). Probably best to get at least 40-50 grams per day.
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7a) Diets low in dietary fiber may underlie or exacerbate constipation, appendicitis, hemorrhoids, deep vein thrombosis, varicose veins, diverticulitis, hiatal hernia, and gastroesophageal reflux (1).
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Table 2. Nutritional drivers of inflammation
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Nutritional drivers of inflammation
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Example of inflammation outcome
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Excess omega-6 fatty acid intake and inadequate omega-3 fatty acids.
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Increased pro-inflammatory cytokines and eicosanoids, with an associated reduction in anti-inflammatory eicosanoids, resolvins, docosatrienes, and neuroprotectins (4-6,13,14).
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Trans fats (partially hydrogenated oils), found in margarine and most packaged foods.
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Raises LDL cholesterol, lipoprotein(a), triglycerides, IL-6, TNF receptor, and IL-1; increase insulin resistance and lipid oxidation; promote fibrin deposition; increase CRP (15-19,68).
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Inadequate potassium
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Hypoxia, free radicals, insulin resistance, tissue acidity and related inflammation (20-23).
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Inadequate magnesium
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Increased excitatory activity in nociceptive pathways, reduced ATP synthesis, increased free radicals, increased release of pro-inflammatory eicosanoids and cytokines, increased CRP, increased expression of syndrome X (24,67,70).
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Inadequate antioxidants
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Increased free radical activity and related inflammation (activation of NFkB, PLA2, COX, LOX) (25,26).
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Inadequate phytonutrients
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Increased free radical activity and related inflammation (activation of NFkB, PLA2, COX, LOX) (25-27)
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Syndrome X – insulin resistance syndrome promoted by: excess body weight; food with a high glycemic index and high glycemic load; reduced magnesium and potassium intake; excess n-6 fatty acids (5,20,28-30).
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Syndrome X and type 2 diabetes increases free radical activity and related inflammation (activation of NFkB, PLA2, COX, LOX) (26).
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Over-eating
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Increased body fat and related cytokine release; increased free radical burden with excess calories (31-33).
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Gliadin – from cereal grains
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Source of occult/overt inflammation and promotes various diseases in susceptible individuals: celiac disease, schizophrenia, ataxia, myopathy, peripheral neuropathy, headaches autism, and Hashimoto’s thyroiditis (34-39,71).
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Lectins – from cereal grains and legumes
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Source of occult/overt damage to the gut, which can lead to increased permeability of bacterial and food antigens, sometimes referred to as leaky gut syndrome (34, 40). Research suggests that lectins may play a role in promoting the following conditions: inflammatory bowel disease, diabetes mellitus, rheumatoid arthritis, glomerulonephritis, psoriasis, multiple sclerosis, retinitis and cataracts, as well as congenital malformations, infertility, allergies and autoimmune problems (41).
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Table 3. Known inflammatory factors and their nutritional modulation
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Known inflammatory factors
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Means of nutritional modulation
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Increased homocysteine – Promotes inflammation and expression of atherosclerosis, Alzheimer’s, Parkinson’s, and osteoporosis (42-47. Available as a blood test.
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Vitamins B6, B12 and folic acid (42,46).
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Increased C-reactive protein – leads to complement activation, adhesion molecules, reduces fibrinolysis, and serves a marker of a generalized chronic inflammatory state (48,49). Available as a blood test.
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Weight loss [fat loss] (49), exercise (50), increased dietary fiber, omega-3 fatty acids, magnesium (51,52,66,67); a multivitamin (68); reducing trans-fats (69); reducing syndrome X/type 2 diabetes 72,73), and improving sleep (74).
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Increased fibrin - Leads to fibrosis and is involved in soft tissue injuries, osteoarthritis, back pain, atherosclerosis, cancer, and others (53-59). Fibrinogen is available as a blood test.
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Reducing n-6 and increasing n-3 (5), reducing syndrome X (53), supplemental proteolytic enzymes (60).
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Increased expression of inducible nitric oxide synthase (iNOS) - Promotes free radical activity and related inflammation (61).
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Turmeric and nutritional factors that reduce NFkB activation (61,62).
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Upregulation of NFkB - NFkB is a pro-inflammatory cell-signaling molecule that increases the expression of PLA2, COX, LOX, iNOS, cytokines, and adhesion molecules (26,62).
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Ginger, turmeric, garlic, red chili, basil, rosemary, fennel, anise, coriander, cloves, pomegrante, green tea, resveratrol, red wine, olive oil, EPA/DHA and food restriction (31-33,61-65).
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Many of the details listed above will not be understood by patients. Even non-researcher healthcare practitioners often struggle with some of these biochemical terms. Fortunately, the correction for pro-inflammatory biochemistry is achieved by adopting an anti-inflammatory eating style. The Deflaming Guidelines and MP3 audio version (link) outline the basic diet and supplement approaches to inflammation reduction.
Additional Resources
I recently wrote three chapters that focus on the relationship among nutrition, inflammation, and musculoskeletal conditions. While the focus in these chapters is musculoskeletal conditions, the same inflammatory state is also known to promote visceral disease.1. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the western diet: Health implications for the 21st century. Am J Clin Nutr. 2005;81:341-54.
2. National Institutes of Health (NIH) website on omega-6 and omega-3 fatty acids.
http://efaeducation.nih.gov/sig/eicosa3.html
3. Mathias JR, Franklin R, QuastDC et al. Relation of endometriosis and neuromuscular disease of the gastrointestinal tract: new insights. Fertility Sterility. 1998; 70:81-88
4. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000; 71(1 Suppl):343S-48S
5. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999; 70(3 Suppl):560S-569S
6. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002; 21:495-505
7. Nettleton J. Omega-3 fatty acids and health. New York: Chapman & Hall; 1995.
8. Calder PC. Dietary fatty acids and the immune system. Nutr Rev 1998; (II):S70-S83.
9. Ford ES, Mokdad AH. Dietary magnesium intake in a national sample of US adults. J Nutr. 2003; 133:2879-82.
10. Vasquez A, Manso G, Cannell J. The clinical importance of vitamin D (cholecalciferal): a paradigm shift with implications for all healthcare providers. Altern Therap 2004; 10:28-36
11. Seaman DR. A sports nutrition: a biochemical view of injury care and prevention. In Hyde TE, Gengenbach MS. Eds. Conservative management of sports injuries. 2nd ed. Boston: Jones and Bartlett; 2007: p.1067-1092
12. Seaman DR. Nutritional considerations for pain and inflammation. In Liebenson CL. Ed. Rehabilitation of the spine: a practitioner’s manual. Baltimore: Williams & Wilkins; 2006: p.728-740
13. Serhan CN. Novel n-3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther 2005; 105:7-21
14. Serhan CN. A search for endogenous mechanisms of anti-inflammation uncovers novel chemical mediators: missing links to resolution. Histochem Cell Biol 2004; 122:305-21
15. Mozaffarian D, Pischon T, Hankinson SE et al. Dietary intake of trans fatty acids and systemic inflammation in women. Am J Clin Nutr. 2004; 79:606-12
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17. Baer DJ, Judd JT, Clevidence BA, Tracy RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Am J Clin Nutr. 2004; 79:969-73
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Effect of hydrogenated and saturated, relative to polyunsaturated, fat on immune and inflammatory responses of adults with moderate hypercholesterolemia. J Lipid Res. 2002; 43:445-52
19. Clifton PM, Keogh JB, Noakes M. Trans fatty acids in adipose tissue and the food supply are associated with myocardial infarction. J Nutr. 2004; 134:874-79
20. Demigne C, Sabboh H, Remesy C, Meneton P. Protective effects of high dietary potassium: nutritional and metabolic aspects. J Nutr. 2004; 134:2903-06
21. Knochel JP. Correlates of potassium exchange. In Seldin DW, Giebisch G. Eds. The regulation of potassium balance. New York: Raven Press; 1989: p. 31-55
22. Knochel JP. Clinical expression of potassium disturbances. In Seldin DW, Giebisch G. Eds. The regulation of potassium balance. New York: Raven Press; 1989: p. 207-240
23. Young DB, Lin H, McCabe RD. Potassium’s cardiovascular protective mechanisms. Am J Physiol 1995; 268:R825-R837
24. Durlach J, Bac P, Bara M, Guiet-Bara A. Physiopathology of symptomatic and latent forms of central nervous hyperexcitability due to magnesium deficiency: a current general scheme. Magnes Res 2000; 13:293-302
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26. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrinol Rev 2002; 23:599-622
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28. Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: more than just syndrome X. Compar Biochem Physiol 2003; 136:95-112
29. Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson JE, Hu FB. Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care. 2004; 27:134-40
30. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002; 5:551-559
31. Otsuka M, Yamaguchi K, Ueki A. Similarities and differences between Alzheimer’s disease and vascular dementia from the viewpoint of nutrition. NY Acad Sci. 2002; 977:155-61
32. Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci. 2002; 57:B211-24
33. Chung HY, Kim HJ, Kim JW, Yu BP. The inflammation hypothesis of aging: molecular modulation by calorie restriction. Ann NY Acad Sci 2001; 928:37-35
34. Cordain L. Cereal grains: humanity’s double edged sword. World Rev Nutr Diet 1999; 84:19-73
35. Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Gruenwald RA, Lobo AJ. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry. 2002; 72:560-63
36. Hadjivassiliou M, Grunewald RA, Kandler RH et al. Neuropathy associated with gluten sensitivity. J Neurol Neurosurg Psych. 2006; 77:126266
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38. van Heel DA, Dart J, Nichols S, Jewell DP, Playford RJ. Novel presentation of coeliac disease after following the Atkins’ low carbohydrate diet. Gut. 2005; 54:1342
39. Knivsberg AM, Reichelt KL, Hoien T, Nodland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002; 5(4):251-61
40. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Brit J Nutr 2000; 83:207-217
41. Freed DLJ. Lectins in food: their importance in health and disease. J Nutr Med. 1991; 2:45-64
42. Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med 2001;39:666-74
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44. Krumdieck CL, Prince CW. Mechanisms of homocysteine toxicity on connective tissues: implications for the morbidity of aging. J Nutr. 2000;130(2S Suppl):365S-368S
45. Miller JW. Homocysteine, folate deficiency, and Parkinson's disease. Nutr Rev. 2002; 60:410-3.
46. Warren CJ. Emergent cardiovascular risk factor: homocysteine. Prog Cardiovasc Nurs 2002; 17:35-41
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50. Geffken D., Cushman M., Burke G., Polak J., Sakkinen P., Tracy R. Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 153: 242-250, 2001
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64. Bellido C, Lopez-Miranda J, Blanco-Colio LM et al. Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men. Am J Clin Nutr. 2004; 80:1487-91
65. Jolly CA, Muthukumar A, Avula CP, Troyer D, Fernandes G. Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr. 2001; 131:2753-60.
66. Ma Y, Griffith JA, Chasan-Taber L et al. Association between dietary fiber and serum C-reactive protein. Am J Clin Nutr 2006;83:760–66.
67. King DE Mainous AG, Geesey ME, Woolson RF. Dietary magnesium and C-reactive protein levels. J AM Coll Nutr. 2005; 3):166-71.L24
68. Church TS, Earnest CP, Wood KA, Kampert JB. Reduction of C-reactive protein levels through use of a multivitamin. Am J Med. 2003;115:702–707.
69. Lopez-Garcia E, SchulzeMB, Meigs JB et al. Consumption of trans fatty acids is related to biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005; 135(3):562-66.
70. He K, Liu K, Daviglus ML, et al. Magnesium intake and incidence of metabolic syndrome among young adults. Circulation 2006;113:1675–82
71. Valentino R, Savastano S, Maglio M et al. Markers of potential coeliac disease in patients with Hashimoto’s thyroiditis European Journal of Endocrinology (2002; 146:479–483.
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74. Meier-Ewert HK, Ridker PM, Rifai N et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004; 43(4):678-83
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