Download The Fire Within

The Fire Within:
The Consequences of Chronic Inflammation
Tieraona Low Dog, MD
Copyright © 2009-­‐2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
Copyright © 2009-2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
“The Fire Within”
• CAD is leading cause of death in United States. • CAD was considered primarily a lipid accumulation mediated disease; now shown to involve an ongoing inflammatory response. Christodoulidis G, et al. Cardiol Rev 2014 Jan 15
Copyright © 2009-­‐2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
Periodontitis and Heart Disease
• Periodontitis recognized as an inflammatory
disease of bacterial origin by American Academy
of Periodontology.
• Plausibility of periodontal bacteria influencing
vascular inflammation strengthened when
Porphyromonas gingivalis isolated from human
atheromatous plaques.
Friedewald VE, et al. J Periodontol 2009; 80:1021-1032
Lower Health Costs?
• Periodontitis closely linked to premature birth, heart disease, diabetes, and other chronic health problems. • Insurance claims 338,891 individuals with medical and dental insurance coverage analyzed in 2011–2013. • Inclusion: (1) diagnosis of at least 1 of 5 specified systemic conditions and (2) evidence of periodontal disease. • Subjects categorized whether they’d completed treatment for periodontal disease in the baseline year, 2005. Jeffcoat MK, et al. American Journal Prev Med 2014; (47)2: 166-­‐74
Significant Benefit
• Outcomes: (1) total allowed medical costs and (2) number of hospitalizations, per subscriber per year, in 2005–2009. • Statistically significant reductions in both outcomes (p<0.05) were found: –
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Type 2 diabetes (40%) Cardiovascular disease (41%) Coronary artery disease (11%) Pregnancy complications (74%) Jeffcoat MK, et al. American Journal Prev Med 2014; (47)2: 166-74
“The Fire Within”
Pre and Probiotics
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Regulate/modulate immune functions.*
Improve intestinal barrier functions.*
Induce hypo-responsiveness to food antigens.*
Support healthy blood glucose levels.*
* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. Copyright © 2009-2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
“Foundations In Herbal Medicine”
Reach for the Prebiotics
• Prebiotics enhance fermentation of the fibers to produce short-­‐chain fatty acids. • These changes are positively correlated with increases in calcium absorption in adolescents and postmenopausal and increases in measures of bone density and strength in animal models Weaver CM, et al. Curr Osteoporos Rep 2015; Jan 25
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Osteoporosis
• Growing evidence osteoporosis may be driven, in part, by chronic low grade inflammation. • Pro-­‐inflammatory cytokines (IL-­‐1, IL-­‐6, TNF-­‐alpha) , accelerate bone loss via activation of osteoclasts, inhibit collagen production in osteoblasts and enhance breakdown of the extracellular matrix. • Large study of older women found almost a 50% increased risk of hip fracture in those with highest levels of inflammatory markers. Barbour KE, et al. J Bone Miner Res 2014; 29(9):2057-­‐64
Osteoarthritis
• Osteoarthritis has an inflammatory component. • Systemic levels of IL-­‐1β, IL-­‐6, TNF-­‐α and CRP rise with the presence of hip or knee OA. • Prospective studies reveal that elevated levels of TNF-­‐α, CRP and IL-­‐6 can predict its progression. • Almost all of these inflammatory mediators regulated by the transcription factor nuclear factor-­‐
κB. Vincent HK, et al. PMR 2012; 4(5 Suppl):S59-­‐67. Copyright © 2013-­‐2015 Integrative Medicine Concepts, LLC. All Rights Reserved.
Auto-­‐Immunity?
• Some researchers believe that constant seeding of bacterial products from the gut leads to synovial inflammation and chronic arthritis in people who are susceptible to auto-­‐immune conditions (e.g., rheumatoid arthritis). Vitetta L, et al. Pathogens 2013; 2(4): 606-­‐626
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Depression and Pain
• Pain is dynamic interplay between central and peripheral nervous system pain processing, HPA axis, cytokines and psychosocial factors. • Multiple studies suggest link between inflammation, depression and pain. • Danish study (>73,000 adults) showed those with highest levels of CRP twice as likely to have psychological distress and depression than those with normal levels. Wium-­‐Anderson MK, et al. JAMA Psychiatry 2013; 70(2):176-­‐184
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Inflammation and Cancer
• Activation of NF-κβ is vital for our body’s ability to
defend itself against infection and is a central
mediator of inflammation.
• Many things activate NF-κβ and when it is
persistently “turned on” it induces genes that are
responsible for increasing cell survival, proliferation,
migration and invasion. It also turns down growth
regulators (e.g., p53) that suppress tumor growth.
Pal S, et al. J Inflamm 2014; Aug 9; 11:23
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“Cancer Prevention in 21st Century”
Pal S, et al. J Inflamm 2014; Aug 9;11:23.
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Factors That Drive Inflammation and Insulin Resistance
Pattern of central obesity Western-­‐dietary pattern, high fructose Sedentary lifestyle, lack of exercise Prolonged psychosocial stress Alterations in gut flora and intestinal permeability • Environmental exposures (smoke, toxins)
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“The Fire Within”
Nurses Health Study
• Healthy (‘prudent’) dietary pattern, characterized by higher intakes of vegetables and fruit, whole grains, fish and legumes, was associated with reduced plasma concentrations of inflammatory markers, including hsCRP and IL-­‐6. • An unhealthy (‘Western’) pattern, high in refined carbohydrates, processed foods, and processed meats was associated with increased inflammatory markers. Lopez-­‐Garcia E, et al. Am J Clin Nutr. 2004;11:1029–1035.
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DASH Diet
• Widely used to reduce hypertension. Reduces risk of metabolic syndrome and type 2 diabetes. • RCT of 48 women with PCOS: there was a statistically significant reduction in serum insulin, hs-­‐CRP, triglycerides, VLDL levels; and waist and hip circumference in 8 weeks. Asemi Z, et al. Horm Metabol Res 2014; June 23
Asemi Z, et al. Nutrition 2014; Mar 15. pii: S0899-­‐9007(14)00142-­‐7. Shirani F, et al. Nutrition 2013; 29(7-­‐8):939-­‐47
Saneei P, et al. Br J Nutr 2013; Dec;110(12):2250-­‐9.
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Low GL diets
High GL diet associated with higher levels of CRP Better weight control (better than low fat) Diabetes prevention, improved blood sugar control More favorable lipid profiles (high glycemic load diets linked to higher triglycerides and lower HDL) Lower heart attack rates (Nurses Health Study) Earlier satiety (demonstrated in well-­‐designed feeding studies) •
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Brand-­‐Miller J, et al. Curr Opin Lipidol 2012; 23(1):62-­‐7
Levitan EB, et al. Metabolism. 2008;11:437–443
Copyright © 2009-2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
Copyright © 2009-2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
• High fructose consumption associated with
increased intestinal permeability, elevated tolllike receptor 4, endotoxemia and development
of non-alcoholic fatty liver disease.
Jin R, et al. Nutrients 2014; 6:3187–3201
Non-­‐alcoholic Fatty Liver Disease
• Small study found significant reductions in
systolic blood pressure, body fat, liver
enzymes (P = .04) and insulin resistance in
children with NAFLD at 3 and 6 months (P
< .05) on a low fructose, low GL diet. • Four week study found low fructose diet in
Hispanic adolescents increased insulin
sensitivity and lowered hs-CRP. Mager DR, et al. JPEN J Parenter Enteral Nutr 2013; Aug 23. Jin R, et al. Nutrients 2014; 6:3187–3201
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The Saturated Fat Debate
• A rigorous analysis of 21 studies determined that there is no significant evidence that dietary saturated fat is associated with an increased risk of coronary heart disease. Siri-­‐Tarino, "Meta-­‐analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease". The American Journal of Clinical Nutrition 2010; 91 (3): 535–46.
Copyright © 2009-­‐2014 Integrative Medicine Concepts, LLC. All Rights Reserved.
Systematic Review
• 12 studies with 7150 participants included.
• No evidence for the beneficial effects of reduced/
modified fat diets in the secondary prevention of
coronary heart disease.
• Recommending higher intakes of polyunsaturated
fatty acids in replacement of saturated fatty acids was
not associated with risk reduction.
Schwingshacki L, et al. BMJ Open 2014; 4(4):e004487.
Annals of Internal Medicine
• Meta-analysis of 76 studies found no basis for
guidelines that advise increased consumption
of polyunsaturated fats to lower your cardiac
risk. The authors concluded:
• "Current evidence does not clearly support
cardiovascular guidelines that encourage high
consumption of polyunsaturated fatty acids and
low consumption of total saturated fats."
Chowdhury R, et al. Ann Intern Med 2014; 160(6):398-406.
The Anti-Inflammatory Diet
Fish & Inflammation
• Research shows that increasing EPA and DHA through
consumption of fatty fish or fish-oil supplements, may
reduce risk of many chronic diseases that involve
inflammatory processes.
• About one-third of Americans eat seafood once a week,
while nearly half eat fish only occasionally or not at all.
Attitudes and Beliefs About Eating Fish: A National Opinion Survey Conducted for The Center for
Food, Nutrition and Agricultural Policy
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Resolvins belong to a family of novel lipid mediators that possess dual anti-inflammatory and pro-resolution actions.
Serhan CN, Chiang N. Curr Opin Pharmacol 2013; 13(4):632-­‐40.
“Dietary Supplements”
Different Types of Fish Oil
• Supplementation is an alternative to eating fish;
however, all supplements are not equal. • Randomized, crossover study of 35 healthy
individuals compared four popular brands/types of
omega 3 fatty acids: –
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Concentrated triglyceride (rTG) Ethyl ester (EE) Phospholipid krill oil (PL) Triglyceride salmon oil (TG) Laidlaw M, et al. Lipids Health Dis 2014; 13:99
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“Dietary Supplements”
Dosing According to Manufacturer’s Recommendations
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“Dietary Supplements”
rTG
EEE
TG
PL
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Foundations In Herbal Medicine
Copyright © 2013-­‐2015 Integrative Medicine Concepts, LLC. All Rights Reserved.
Herbs For Inflammation • There are many but some of primary herbs to consider include: –
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Turmeric Boswellia Ginger Guduchi Devil’s Claw Cat’s Claw Chinese skullcap Licorice Salix containing plants
Copyright © 2013-­‐2015 Integrative Medicine Concepts, LLC. All Rights Reserved.
Turmeric (Curcuma longa)
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Turmeric
• Long history in Ayurvedic medicine. • Mediates anti-­‐inflammatory effects through down-­‐
regulation of inflammatory transcription factors, cytokines, protein kinases, and enzymes.* • Multiple studies show that curcumin alone and in combination with boswellia, ginger, and other herbs has beneficial effects.* Shehzad A, et al. Biofactors 2013; 39(1):69-­‐77. * These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. Copyright © 2013-­‐2015 Integrative Medicine Concepts, LLC. All Rights Reserved.
Foundations In Herbal Medicine
Copyright © 2013-­‐2015 Integrative Medicine Concepts, LLC. All Rights Reserved.
Absorption
• Improved curcumin properties;, tissue distribution and bioavailability can be achieved with addition of piperine. • Other methods to increase bioavailability include liposomal, nanoparticulated and phospholipid complex formulations of curcumin. • Doses up to 12 grams per day not associated with toxicity HOWEVER, GI upset is common complaint. • Dose generally 1200 mg per day, divided doses. Bisht S, et al. Curr Drug Discov Technol. 2009;6(3):192-­‐9. Kakarala M, et al. Breast Cancer Res Treat 2009; 122:777-­‐785
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“The Fire Within”
Summary
• Recognize the powerful role inflammation plays in chronic disease. • Diet should be heavily weighted to vegetables/
fruits, healthy proteins and fats including omega 3, limited processed foods. • Most patients should be on daily turmeric, pre/probiotic, omega 3 fatty acids and a multivitamin.
Copyright © 2009-­‐2014 Integrative Medicine Concepts, LLC. All Rights Reserved.