Anti-Inflammatory Diets for the Prevention of Chronic Disease
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1 Anti-Inflammatory Diets for the Prevention of Chronic Disease Jessica A. Miller, PhD R25T Cancer Prevention and Control Postdoctoral Fellow The University of Arizona Cancer Center May 9, 2013
2 Objectives Define inflammation Describe how inflammation relates to chronic diseases. Identify role of macronutrients (carbohydrates, fat, protein) in either promoting or suppressing inflammation. Identify role of micronutrients (vitamins, minerals, bioactive food components) in either promoting or suppressing inflammation.
3 Inflammation Definition: a protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues. Acute inflammation: usually of sudden onset, marked by the classical signs, in which vascular and exudative processes predominate. Classical signs: pain, heat, redness, swelling, and loss of function Chronic inflammation: may have a rapid or slow onset but is characterized primarily by its persistence and lack of clear resolution; it occurs when the tissues are unable to overcome the effects of the injuring agent.
4 Apoptosis Phagocytosis Cytokine/chemokine scavenging Lymphatic drainage Macrophage recruitment Key Molecular Regulators: Prostaglandins Leukotrienes Cytokines Chronic diseases Adapted from: Serhan CN, AJP October 2010, Vol. 177, No. 4:
5 Breast Freund A. Trends Mol Med May ; 16(5):
6 Overweight and Obesity Inflammation and Chronic Disease Promotion 70% Americans are overweight (BMI 25) or obese (BMI 30) World Health Organization predicts by 2030 Cancer Hallmarks 45% Cancer deaths 34% Arthritis >50% Type 2 diabetes (7th leading cause of death) 50% NAFLD 100% Dementia Alosco ML, Obesity (Silver Spring) Apr 27. Hanahan and Weinberg, Cell (2011) 5 :646-74
7 Obesity FFA uptake extramyocellular adipose Macrophage activation/recruitment Adipocyte hypertrophy Macrophage recruitment Macrophage polarity switch cytokine production (adipokines) lypolysis ER stress Systemic IR and inflammation Steatosis Kuppffer cell activation Cytokine production ER stress Olefsky JM and Glass CK Annu. Rev. Physiol :219 46
8 Levels of human networks Arthritis Social network Cancer Obesity Diabetes Disease network Inflammatory network Barabási AL et al N Engl J Med (2007) 357:
9
10 Macronutrients Carbohydrates (4 Cal/g) 50-60% caloric intake Protein (4 Cal/g) 1-2 g/kg body weight Fat (9 Cal/g) <30% caloric intake
11 Carbohydrates Good Carbs (complex carbohydrates): Starches: whole wheat pasta, rice, cereals, potatoes, corn, peas, legumes (pinto beans) Fruits Vegetables Dairy Products (milk & yogurt) Bad Carbs (anything processed): candy, chips, cookies, ice cream, etc.
12 Benefits of Complex Carbohydrates Fuel Source 4 calories/gram Need glucose for your brain! Metabolic products: energy, CO 2, H 2 O inflammation insulin resistance fasting glucose BMI Whole grain intake: 20-40% risk in CAD 20-30% in diabetes 20-30% total mortality Other micronutrients present in complex carbohydrate sources Cochrane Database Reviews, 2008;Jan 23
13 Simple Carbohydrates Lead to Inflammation Refined Carbohydrates Loss of fiber, vitamins, minerals, phytonutrients & essential fatty acids Result rapid swings in blood glucose & insulin; hunger and serum fatty acid levels Acute hyperglycemia Impaired endothelial function NF- B transcription activated free radicals & inflammatory cytokines J Xu and M-H Zou, Circulation. 2009;120:
14 Protein Fuel source 4 calories/gram 2 g/kg body weight lean protein diets associated with: body fat % blood pressure serum lipid levels fasting glucose levels glycemic control risk for CAD, CHF, MI, and Stroke Plant proteins: Legumes Soy protein Whole grains Nuts Animal proteins: Meat, chicken or fish Eggs Cheese Milk
15 Fat Saturated: lard, butter, cheese, animal proteins Trans-fatty acids: Processed foods Monounsaturated: olive oil, olives, avocados & most nuts Polyunsaturated (Ω-6 and Ω-3) Essential: we can t produce Linoleic Acid (Ω-6): nuts,vegetable oils Linolenic Acid (Ω-3): vegetable oils, cold-water fish, soybeans, flaxseeds, canola oil & walnuts Non-Essential: endogenous Arachidonic Acid (Ω-6): chicken, beef, pork DHA (Ω-3): fish
16 Benefits-Healthy Fat Consumption Fuel Source 9 calories/gram Monounsaturated (oleic acid) and polyunsaturated (Ω-3 and Ω-6) fatty acids Rates of CAD Blood pressure T-chol & LDL-C Ω-3 Anti-inflammatory Anti-cancer effects (BC, CRC) RA & IBD neurodegenerative disorders Ω-6:Ω-3 ratio 5:1 = beneficial effects Western diet 15:1 = chronic inflammation AP Simopoulos, Experimental Biology and Medicine 2008, 233:
17 Impact of Unhealthy Fat Saturated Fats: T-cholesterol, LDL-C, glucose, triglyceride, inflammatory markers; insulin sensitivity Monounaturated Trans-Fats: T-cholesterol, LDL-C, inflammatory biomarkers; HDL-C levels Western diet 15:1 (Ω-6:Ω-3 )= chronic inflammation PGE 2
18 Fatty meal, stress, inflammation, mitogens NSAIDs Cyclooxgenase (COX) Lipoxygenase (LOX) Cytochrome P450 COX-1 COX-2 15-LOX 12-LOX 5-LOX CYP4A CYP2C8 (CYP) CYP2C9 CYP2J Prostaglandin PGE s 2 PGD 2 Inflammation Pain Proliferation Chemokine production VEGF synthesis Survival Migration Invasion b-fgf synthesis (Prostacyclins and Thromboxanes Lipoxins LxA 4 LxB 4 Anti-Inflammation Allergy Bronchoconstriction n-hetes 20-HETE Leukotrieness LTA 4 LTB 4 LTC 4 LTD 4 Inflammation Inflammation Blood pressure Vascular Function Pain Dominates in obesity and diabetes EET Diols Inflammation seh Epoxyeicosatrienoic acid 5,6-EET 8,9-EET 11,12-EET 14,15-EET Decrease Inflammation Vasorelaxation Cardioprotection
19 Chronic Diseases Associated Ω-6 metabolites (PGE 2 ) Cancer (solid tumors) Asthma Rheumatoid arthritis Chronic obstructive pulmonary disease (COPD) Cardiovascular Disease
20 Omega-3 (EPA/DHA) Cyclooxgenase (COX) Lipoxygenase (LOX) Cytochrome P450 COX-1 COX-2 15-LOX 12-LOX 5-LOX CYP4A CYP2C8 (CYP) CYP2C9 CYP2J Prostaglandin PGE s 3 PGI 2 Anti-Inflammatory Reduce Pain Reduce chemokine production Thromboxanes Lipoxins Leukotrieness LTB 5 LTC 5 Anti-Inflammatory Reduce Pain Reduce chemokine production 20-HEPE 22-HDHE 17,18-EETeTr 19,20-EDP Decrease Inflammation Vasorelaxation Cardioprotection More potent than EET s Improve vascular f(x) Adapted from: C Arnold, Pharmacological Reports 2010, Vol. 62, 536
21 Big Picture Adipokines Micronutrients (Vitamins, minerals) Bioactive Food Components (limonene, resveratrol, EGCG, flavonoids, etc)
22 Big Picture Micronutrients (Vitamins, minerals) Bioactive Food Components (limonene, resveratrol, EGCG, flavonoids, etc)
23 Micronutrients with Antioxidant Activity Vitamins: Ascorbic Acid (Vitamin C) Tocopherols and Tocotrienols (α-tocopherol: Vitamin E) Carotenoids (Vitamin A) Minerals: Magnesium Selenium (required for other antioxidants) Zinc (required for other antioxidants) Other micronutrients Melatonin (hormone)
24 Bioactive Food Components 25,000 known BAFC in food supply Anti-inflammatory action through multiple mechanisms (ROS scavenging) limonene
25 An argument for coffee: Alzheimer s protection Coffee drinkers less likely to develop type 2 diabetes, stroke, depression, death from any cause, and neurodegenerative diseases, including Parkinson's and Alzheimer's Coffee contains polyphenols and other antioxidants Free radical scavenging Regenerated axons and dendrites
26 Mediterranean Diet Olive oil (Ω-3) More fish, less red meat (i.e. more Ω-3) Healthy grains and plant proteins Bread (whole wheat/whole grain) Abundance of fruit and vegetables Red wine Coffee! Caution in reductionist approach
27 Selenium/Vitamin E Cancer Prevention Trial (SELECT): 2008 >35,000 men Vit E dose: (400 IU/d) Vitamin E Selenium Placebo Selenium + Vitamin E in prostate cancer in Vit E group compared to placebo (P=0.06) Vit E invervention halted: 2008 Lippman SM, JAMA, January 7, 2009 Vol 301, No. 1; 39-51
28 SELCT Trial: Follow up 2011 >50% of individuals 60 years or older are taking supplements containing vitamin E 23% of them are taking at least 400 IU/d despite a recommended daily dietary allowance of only 22.4 IU for adult men Klein EA. et al JAMA, October 12, 2011 Vol 306, No
29 Vitamin E supplementation and other chronic disease? Modest benefit: Alzheimer disease (as 1 part of a combination of oral antioxidants) Age-related macular degeneration No benefit: Prevention of cardiac events Overall mortality Colorectal adenomas Respiratory infections in elderly individuals Preeclampsia in women with type 1 diabetes Prevention of cataracts or macular degeneration Klein EA. et al JAMA, October 12, 2011 Vol 306, No (references within)
30 General Multivitamin? Iowa Women s Health Study (observational cohort 38,772): risk of overall mortality with daily multivitamin in elderly women Physicians Health Study (N=14,641): (randomized double-blind placebo control trial) risk cancer incidence 8% cancer mortality Risk of clinically advanced prostate cancer with 400 IU/d Vit E Women s Health Initiative: any cancer Nurses Health Study: risk colon cancer after 15 years Swedish Study (N=35,000 women): risk of breast cancer Greenlee H et al J Altern Complement Med Aug;10(4): Peters U, Cancer Causes Control Feb;19(1): Epub 2007 Oct 18
31 Vitamins and Lifestyle (VITAL) study cohort 75,288 men and women Specifically looked at multivitamins and other supplements Findings Multivitamins risk of breast cancer Cranberry pills (Vitamin C) bladder cancer 3.44 (1.86, 6.35) Zinc ovarian cancer 2.19 (1.41, 3.40) Soy (multiple antioxidants) prostate cancer 1.99 (1.38, 2.87) Melatonin cervical cancer 1.86 (1.19, 2.90) Vitamin D thyroid cancer 1.66 (1.21, 2.28)
32 Final Recommendations Diet matters! Chose Whole grains over white flour Lean meat (especially fish) Unsaturated fat Variety of fruit and vegetables Supplements should be treated like drugs Ask patients about supplement use Research side-effects of supplements you might recommend
33 Multiple Choice Questions 1. What is the best fat? A. Saturated Fat B. Trans Fat C. Monounsaturated Fat D. Polyunsaturated Fat
34 Multiple Choice Questions 2. Inflammation causes which diseases: A. Obesity B. Diabetes C. Cancer D. None of the above
35 Multiple Choice Questions 3. Which is NOT a molecular regulator of inflammation? A. Prostaglandins B. Leukotrienes C. Cytokines D. Cholesterol
36 Multiple Choice Questions 4. If a patient asks about XX supplement for XX disease/pain/beauty concern should you: A. Tell them not to take it B. Tell them go ahead and take it C. Inquire about their diet to see if they are already getting adequate levels D. Measure blood levels
37 Something to Think About Why was supplementation with the Ω-3 fatty acid, EPA a success in preventing polyps, while supplementation with Vitamin E was a failure and promoted prostate cancer?
38 Questions?
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