Inflammation & Chronic DiseasesBy: Whitney Eichsteadt, UW-Green Bay Dietetic Intern

(Email: eichwl11@uwgb.edu)

Presentation Objectives

• Definition of inflammation• Difference between Acute & Chronic Inflammation • Promotion of disease and inflammation• Inflammation & Type 2 Diabetes study• Inflammation & Cancer study• Inflammation & Obesity study• Food sources• Main Takeaways• Professional Opinion• Take Home Message/Summary

What is inflammation?• Immune system’s first response to:• Infection• Injury• Irritation

• Diseases resulting from inflammation:• Cancer• Diabetes• Cardiovascular disease • Alzheimer’s and Parkinson’s disease• Non-alcoholic fatty liver disease

Acute Inflammation vs Chronic Inflammation• Acute Inflammation: initial response to pathogen–or damage-associated molecular patterns

• Chronic Inflammation: occurs when the initial inflammation continues due to: • Persistence of the harmful source• Exaggerated inflammatory response• Impaired resolution program

Chronic inflammation is the result of prolonged white blood cells attacking nearby healthy tissues; immune system is consistently fighting itself.

How does inflammation promote disease?

• Inflammasome: innate immune system receptors and sensors• Senescent cells: skin and adipose tissues -> complex stress response that mediates tissue

repair and remodeling• The Microbiota: affects cancer progression and treatment efficacy • Activation of microglia: plays vital role in the etiology & progression of age-related

neurodegenerative diseases • Localized infection: infection in one area can lead to a dysbiotic relationship with another

Inflammation & Diabetes

Inflammation & Type 2 Diabetes• Inflammation and T2DM relationship:

• Pathogenesis of insulin resistance -> leads to T2DM & related complications• High glucose levels promote:

1) Proinflammatory cytokine release 2) Elevates surface protein expression of toll-like receptor (TLR)3) Promotes proinflammatory signaling pathways4) Causes the release of proinflammatory microparticles (MPs) in monocytes/macrophages

High glucose levels trigger the activation of innate immune cells = drives the cycle of inflammation & insulin release in Type 2 Diabetes.

“The effect of a short-term low-

carbohydrate, high-fat diet with or without postmeal walks on

glycemic control and inflammation in type

2 diabetes: a randomized trial”

• Study Design: Randomized Control Trial• N=16 (8 men, 8 women), aged between 48 and 72

y.o. • Inclusion Criteria: Individuals with physician-

diagnosed T2DM, HbA1c >6.5%, fasting plasma glucose >70mmol/L, or 2-hour glucose oral glucose tolerance test >11.1 mmol/L• Exclusion Criteria: Individuals involved in a

regular exercise routine (> 3 days of structured exercise per week), already following a low carb, high-fat diet (LCHF), unwilling to consume the provided meat-containing diets, cannot be on insulin, or have diagnosis of any cardiovascular, kidney, or diabetic complications.

Type 2 Diabetes study continued…

Purpose:

To determine whether reducing hyperglycemia with an LCHF diet could lower

markers of innate immune cell activation and systemic inflammation in people with

T2DM.

Method/Intervention:

• 3 short-term (4-days) controlled-intervention periods: 1) Low-fat Low-GI diet (GL)- control group , 2) Low-carb high-fat diet (LC), 3) LC with 15-min post meal walks (LC + Ex)

• Fasting blood samples and step trackers used to monitor results from intervention

• 9-14 days “wash-out period”

Type 2 Diabetes study continued…

• Results:

• A LCHF diet with or without postmeal walks improved four-day glycemic control compared with a GL diet.

• There were no consistent effects of the individual interventions on inflammatory markers but overall, all 3 diets showed to lower PBMC p-JNK over the short-term.

• MCP-1 was the only cytokine to show a significant decrease over the 4-day interventions.

Limitations & Strengths

Limitations:1) Some unintended weight loss ( ~1-2 kg) in all

intervention, 2) participants continued medications during study, and 3) the

overall length of the study

Strengths: Proved that a Low carb-High fat diet with and without

postmeal walks significantly and rapidly normalized blood glucose

levels.

Inflammation & Breast Cancer

Inflammation & Breast Cancer• Breast Cancer survivors (BCS) are the largest number of cancer survivors

• Weight = primary intervention to prevent recurrence and cardiovascular disease & diabetes • Anti-inflammatory diet: found to reducing risk of comorbidities

• Mediterranean diet shown to help lower inflammatory markers and lower mortality in Cancer, T2DM, Cardiovascular Disease, and cognitive decline.

• Herbs & spices found to contain polyphenols and other antioxidants -> strong antagonists against tumorigenesis, carcinogen bioactivation, & inflammation.

“Dietary intervention among breast cancer survivors increased

adherence to a, Mediterranean-style,

anti-inflammatory dietary pattern: The Rx

for Better Breast Health Randomized

Controlled Trial”

• Study design: Randomized Control Trial • N= 125 breast cancer survivors (60= intervention,

65=control)• Inclusion criteria: Overweight or obese (BMI:

>/= 25), early stage of cancer (0-III), English-speaking, completed treatment at least 2 months prior to study enrollment• Exclusion criteria: BMI < 25, treatment < 2

months prior to start of enrollment, stage 4 cancer

Breast Cancer study continued… Purpose:

Education and culinary-based dietary intervention to increase adherence to a Mediterranean-style, anti-inflammatory dietary pattern in breast cancer survivors (BCS) by promoting consumption of anti-

inflammatory foods, herbs, and spices.

Method/Intervention:

• 6-month intervention including:• Monthly nutrition and cooking workshops• Motivational Interviewing phone calls• Individualized newsletters• Control group: received monthly

informational brochures but no navigational services

• Dietary intakes were collected via questionnaire and 3-day food records at baseline and 6 months

Breast Cancer study continued… • Results: • Adherence to Mediterranean diet guidelines significantly increased in the intervention group.

• 3 areas of greatest improvement when study concluded:• Consuming >/= 3 servings of fish or shellfish/week• Reducing red meat intake to < 1 serving/per day• Limiting consumption of commercial sweets & baked goods to < 3 times/per week

• Consumption/use of herbs and spices significantly increased.

Limitations & Strengths

Limitations: Assessments of dietary intake were based on self-report from participants, missing data was found

from food records, nutrient biomarker not used, and length of intervention

period

Strengths: Moderate sample size w/ low attrition rates, diverse sample size

(over 50% Latinas), and focused on promoting a dietary pattern rather

than a specific food group or nutrient

Inflammation & Obesity

Inflammation & Obesity• Poor diet = leading risk factor for premature death & disability in the United States

• Metabolic syndrome, Heart Disease, and Diabetes

• Fruits & vegetables (FV) and/or whole grains (WG) can have significant impacts on markers of metabolic syndrome.

• Metabolic benefits of FV & WG interacts with the gut microbiota: • Short chain fatty acid (SCFA) production • SCFA are signaling molecules for carbohydrate & lipid metabolism

Increased SCFA = decreased risk for cancer and obesity

“Role of whole grains versus fruits and

vegetables in reducing subclinical

inflammation and promoting

gastrointestinal health in individuals affected

by overweight and obesity: a randomized

controlled trial”

• Study Design: Randomized controlled trial• N= 49 (19 M, 30 F)• Inclusion criteria: BMI > 25, no diagnosed GI

diseases, no antibiotic use for 3 months before start of enrollment, < 1 hour/per week of structured exercise, and low intake of FV & WG• Exclusion criteria: BMI < 25, high intake of FV

or WG, regular structured exercise, recent antibiotic use, health reasons, or scheduling conflicts

Obesity study continued…

Purpose:

To determine the impact of increasing intake of either WG or FV on inflammatory markers and

gut microbiota composition.

Method/Intervention: • Participants randomized into three groups: 1) 3

servings/per day of WG, 2) 3 servings/per day of FV and 3) control (refined grains); diet diaries for all groups

• Stool & blood samples collected at baseline and 6 weeks

• Inflammatory markers measured: TNF-∝, IL-6, LBP, and hs-CRP

• Stool sample analysis included short/branched chain FAs and microbiota composition

Obesity study continued…• Results:• Significant decrease in LBP in WG and FV groups

• FV diet induced a significant change in IL-6

• WG diet showed a significant decrease in TNF-∝

• Individualized changes were seen in microbiota composition but differences between treatment groups was not identified.

Limitations & Strengths

Limitations: Subjects did not all consume the same foods (they could

choose from specific groups), relied on diet diaries to monitor treatment

compliance, and variety of foods in study

Strengths: Had comparison of WG and FV as focus of study, showed

positive impact that WG and FV intake can have on metabolic health for those that normally have low intake of WG &

FV.

Anti-Inflammatory Food SourcesFood sources:

• Focus on:• Berries• Fatty fish• Cruciferous vegetables• Whole grains• Peppers

• Limit added sugars, refined carbs, processed meats, and fried foods.

Anti-Inflammatory herbs & spices:• Cinnamon: polyphenols and

cinnamaldehyde -> anti-tumor properties & anti-inflammatory properties

• Garlic: limits effects of pro-inflammatory cytokines

• Ginger: antioxidant and anticancer properties

• Black pepper: antibacterial and antioxidant• Rosemary: antioxidant -> boost immune

system, improve blood circulation

• Green tea• EVOO• Grapes• Mushrooms• Avocado

Main Takeaways

Inflammation is a natural response our

body uses for protection.

1Connection to many

chronic diseases.

2There is no one food

to “fix all”.

3Many areas for future

research.

4

Professional Opinion

Inflammation is a complex process in our bodies; direct relationship to chronic disease

progression.

Nutrition interventions are beneficial at all parts of disease progression.

Food sources combined with herbs & spices work together to reach optimum benefits.

Take Home Message

(1) Inflammation increases as we age, but research that shows strong benefits to a healthful diet filled with a variety of fruits, vegetables and cooking with herbs and spices.

(2) Lots of research to comb through; area of research that consistently has different viewpoints to explore.

(3) Inflammation affects all systems of the body.

(4) Understanding the process of inflammation and how to educate target population can result in long-term changes.

Questions?

References• Kopf JC, Suhr MJ, Clarke J, et al. Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in

individuals affected by overweight and obesity: a randomized controlled trial. Nutr J. 2018;17(1):72. Published 2018 Jul 30. doi:10.1186/s12937-018-0381-7• Margină, D., Ungurianu, A., Purdel, C., Nițulescu, G. M., Tsoukalas, D., Sarandi, E., Thanasoula, M., Burykina, T. I., Tekos, F., Buha, A., Nikitovic, D., Kouretas, D., &

Tsatsakis, A. M. (2020). Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 143, 111558. https://doi.org/10.1016/j.fct.2020.111558

• Myette-Côté, É, Durrer, C., Neudorf, H., Bammert, T. D., Botezelli, J. D., Johnson, J. D., . . . Little, J. P. (2018). The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: A randomized trial. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 315(6). doi:10.1152/ajpregu.00240.2018

• Zuniga, K. E., Parma, D. L., Muñoz, E., Spaniol, M., Wargovich, M., & Ramirez, A. G. (2018). Dietary intervention among breast cancer survivors increased adherence to a Mediterranean-style, anti-inflammatory dietary pattern: The Rx for Better Breast Health Randomized Controlled Trial. Breast Cancer Research and Treatment, 173(1), 145-154. doi:10.1007/s10549-018-4982-9

• Kopf, J. C., Suhr, M. J., Clarke, J., Eyun, S., Riethoven, J. M., Ramer-Tait, A. E., & Rose, D. J. (2018). Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: A randomized controlled trial. Nutrition Journal, 17(1). doi:10.1186/s12937-018-0381-7

• Publishing, H. H. (n.d.). Understanding acute and chronic inflammation. Retrieved from https://www.health.harvard.edu/staying-healthy/understanding-acute-and-chronic-inflammation