The Nutrition-Inflammation Connection

by Nilima Desai, MPH, RD

Research has established that inflammation is a risk factor for several chronic conditions such as diabetes, cardiovascular disease, arthritis, inflammatory bowel disease, and metabolic syndrome.¹ But understanding how inflammation works can be overwhelming.

Types of Inflammation

Inflammation is classified as either acute or chronic. Inflammation is a natural and necessary component of innate immunity since acute inflammation is the normal physiologic response to injury, infection, or irritation¹ and is often short-lived. This acute inflammatory process leads to the elimination of toxins, repairs damaged tissue,¹ and helps restore homeostasis at the damaged site. The resolution of inflammation is an active process that involves cytokines and other anti-inflammatory signals, such as lipid-derived mediators, rather than the pro-inflammatory pathways simply being switched off.¹

Chronic inflammation results from a breakdown of normal processes that regulate inflammation; these include both anti-inflammatory and pro-resolving pathways. Chronic inflammation is a long-term physiologic response to components such as poor nutrition, stress, viral infection, and environmental toxins. This chronic, low-grade inflammatory state can be “silent,” going undetected for years without manifesting any signs or symptoms, causing organ damage, which may lead to a myriad of health conditions.

Nutrition and Inflammation

Diet may play a central role in the regulation of chronic inflammation.² Balancing the intake of pro-inflammatory vs. anti-inflammatory nutrients may impact systemic inflammation levels. Many epidemiological and experimental trials have linked certain nutrients and dietary patterns to inflammation promotion in the body through oxidative stress, upregulating pro-inflammatory mediator nuclear factor-kappa B and activating cytokine production.^2,3

Pro-inflammatory Nutrients

1. Saturated fatty acids: The 1999-2000 National Health and Nutrition Examination survey (NHANES) data revealed a modest association between saturated fat intake (present in foods such as red meats, full-fat dairy, fast food meals, etc.) and elevated C-reactive protein (CRP) levels, which is a biomarker of inflammation.⁴ In vitro studies have shown a correlation between saturated fatty acid intake and an increase in pro-inflammatory cytokines such as IL-6, and TNF-α.⁵

2. Trans fatty acids: Artificial or hydrogenated trans fats, found in cookies, chips, and other processed snacks, have been linked with increased cardiovascular disease because they tend to increase LDL (“bad” cholesterol) but do not increase HDL (“good” cholesterol). In an analysis of the Nurses’ Health Study follow-up cohort, there was a 73% higher level of CRP in women who were in the highest quintile of trans fat intake compared with the lowest quintile, and IL-6 levels were 17% higher.⁶

3. Imbalance in omega-6 to omega-3 fatty acid ratio: The evolution of the Western diet over the years has prompted a rise in the overconsumption of refined vegetable oils rich in omega-6 fatty acids, creating an imbalance in the ratio of omega-6 to omega-3 fatty acids. Omega-6 fatty acids are precursors to pro-inflammatory eicosanoids and are active in the inflammatory process. Excessive amounts of omega-6 fatty acids and a high omega-6 to omega-3 ratio (20:1) have been found to promote several inflammatory and autoimmune diseases.⁷ The preferred ratio of omega-6 to omega-3 for optimal health is 1:2/1.⁷

4. High refined carbohydrate intake: Refined carbohydrates such as white bread, rice, pasta, juice, sodas, desserts, etc., are highly processed, resulting in the removal of fiber, vitamins, minerals, and phytonutrients. Prolonged, high intake of refined carbohydrates can lead to rapid swings in blood glucose levels and acute hyperglycemia. Studies indicate that this acute hyperglycemia may increase circulating levels of free radicals and pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-18.⁹

Another observational study found a positive association between high saturated and trans fat intake from processed and red meats, full-fat dairy products, high-glycemic carbohydrates such as French fries, desserts, etc., in the Western diet, and inflammation.¹⁰

Anti-inflammatory Nutrients

1. Polyphenols are naturally occurring plant compounds with numerous biological activities, which are found in fruits, vegetables, herbs, spices, cereals, and beverages such as coffee and tea. There are about 8,000 phenolic compounds that have been identified in plants¹¹ and are categorized into four different classes.^11,12 These classes are the phenolic acids, flavonoids, stilbenes, and lignans. Foods such as strawberries, raspberries, black radish, curcumin, and tea contain phenolic acids.¹³ Quercetin and kaempferol are the main types of flavonoids, which are found in onions, kale, leeks, broccoli, and blueberries.¹³ Flavonoids are also present in citrus fruits, millet, wheat, soy, red wine, green tea, and chocolate.¹³ Linseed is the richest dietary source of lignans, with lentils, cereals, garlic, and pears as being a minor source.¹³ Resveratrol, a stilbenoid, has been widely studied for its anti-oxidative property and is present in low quantities in red wine.¹³

Several in vitro and in vivo studies suggest that polyphenols enhance antioxidant activity, inhibit pro-inflammatory cytokines, and prevent free radical formation.¹⁴

2. Dietary fiber is described as a carbohydrate that is not absorbed or digested in the small intestine. There are two types of fiber; both are equally important due to the many positive health benefits that are associated with them. Soluble fiber includes gums, pectins, psyllium, and beta-glucans. Food sources include legumes, asparagus, Brussels sprouts, oats, and flax seeds. Insoluble fiber includes lignin and cellulose. Food sources include cabbage, onions, whole grain, wheat bran, dried fruits, etc.

One of the health benefits associated with fiber is its role in combating inflammation. Several epidemiological studies suggest that fiber intake reduces the risk of obesity, and high fiber intake leads to less inflammation, as indicated by lower plasma CRP levels.¹⁵ Clinical trials with fiber supplementation in patients with inflammatory bowel disease (IBD) resulted in reduced IL-6 levels and increased IL-10 (anti-inflammatory marker) levels in dendritic cells of patients with Crohn’s disease compared to placebo.¹⁵

3. Polyunsaturated omega-3 fatty acids (EPA and DHA) are essential and found in fatty fish such as salmon, mackerel, halibut, tuna, algae, and krill and some plant oils. EPA and DHA interfere with arachidonic acid metabolism, which once oxygenated can be transformed into prostaglandins and leukotrienes that can modulate inflammatory reactions. EPA and DHA also form pro-resolving lipid mediators, which can inhibit pro-inflammatory pathways and are critical to the resolution of inflammation.¹⁶

It was noted in the Nurses’ Health Study that there were lower concentrations of CRP, IL-6, and E-selectin, which are markers of inflammation, in the quintile of highest omega-3 intake compared with those in the lowest quintile.⁹ In another study, supplementation with alpha-linolenic acid (ALA) in 50 dyslipidemic patients significantly decreased CRP and IL-6 levels.⁹

One of the best ways to fight inflammation lies in your pantry, not the medicine cabinet! Here are some suggestions on incorporating anti-inflammatory foods in your diet:

1. Make your plate colorful!
2. Include 5 servings of green leafy and cruciferous vegetables a day.
3. Add 1 cup of raspberries or blueberries to your morning smoothie.
4. Add fresh turmeric or ginger to your freshly squeezed vegetable juice.
5. Eat more lentils and beans by making a nice vegetable soup or stew.
6. Keep nuts like walnuts handy for a quick snack.
7. Add 1-2 Tbsp. flax and chia seeds in your oatmeal.
8. Aim for at least 1-2 servings of omega-3 rich fish per week.
9. Incorporate flavorful whole grains, like oatmeal and brown rice.
10. Shop the perimeter of the grocery store, where you find most of the fresh, whole foods.

References:

1. Minihane AM et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr. 2015;114(7):999-1012.
2. Xu H et al. A proinflammatory diet is associated with systemic inflammation and reduced kidney function in elderly adults. J Nutr. 2015;145(4):729-735.
3. Kiecolt-Glaser JK. Stress, food, and inflammation: Psychoneuroimmunology and nutrition at the cutting edge. Psychosom Med. 2010;72(4):365-369.
4. King DE et al. Relation of dietary fat and fiber to elevation of C-reactive protein. Am J Cardiol. 2003; 92:1335-1339.
5. Chait A et al. Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol. 2010;30(4):692-693.
6. Lopez-Garcia E et al. Consumption of Trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005;135(3):562-566.
7. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56(8):365-379.
8. Simopoulos AP. The importance of a balanced omega-6 to omega-3 ratio in the prevention and management of obesity. Open Heart. 2016;3(2):e000385
9. Giugliano D et al. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006;48(4):677-685.
10. Fung TT et al. Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am J Clin Nutr. 2001;73:61-67.
11. Hussain T et al. Oxidative stress and inflammation: what polyphenols can do for us? Oxid Med Cell Longev. 2016; 2016: 7432797
12. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010;2(12):1231-1246.
13. Manach C et al. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004; 79(5):727-747.
14. Zhang H et al. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr Opin Food Sci. 2016; 8:33-42.
15. Shiu-Ming K. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr. 2013;4:16-28.
16. Serhan CN et al. Resolvins and protectins in inflammation-resolution. Chem Rev. 2011; 111(10):5922-5943.

Nilima Desai, MPH, RD

Nilima Desai is Sr. Manager of Medical Marketing and Metagenics Institute. Nilima is a Registered Dietitian (RD) who received her undergraduate degree from California State University Long Beach in Nutrition and Dietetics and her Master’s in Public Health Nutrition from Loma Linda University. She has over 14 years of experience delivering medical nutrition therapy in the areas of diabetes, renal disease, weight management, and vegetarian nutrition. She also served on the board of the Renal Practice Group of the Academy of Nutrition and Dietetics from 2012-2016 as the Membership Chair. In her free time she runs half marathons and shuttles her two kids to their activities.