Dr. Tim Says....

Inflammation

Inflammation is the body's response to things that might cause damage: this might include dysfunctional cells, invading foreign agents (like a virus or a bacteria) or exposure to toxins. The purpose of inflammation is to attract immune cells to destroy the damaging invader and return the tissue to normal. Acute inflammation is a temporary response, with the probably familiar signs of heat, redness, swelling, pain, and perhaps loss of function.¹

When acute inflammation fails to repair the tissue, chronic inflammation occurs. Inflammatory cells, particularly lymphocytes, macrophages, and plasma cells, become overactive. Macrophages, for example, produce a substance known as cytokine that in essence causes a chain reaction of more inflammation, which can ultimately damage not just individual cells, but also tissues and whole organ systems. Unlike acute inflammation, you can't usually feel the damage chronic inflammation is doing to your body. This chronic inflammation plays a role in almost all of the top causes of mortality in the U.S..²

The Typical Western Diet Leads to Chronic Inflammation

Inflammatory foods, harmful chemicals, artificial preservatives, smoking, stress, lack of sleep, and excess body fat promote a state of oxidative stress (which is an imbalance between free radicals, which damage cells, and the body's ability to counteract them) within the body. Excessive free radicals damage the cells and lead to chronic inflammation.³ Diet has a significant effect on the body's level of inflammation: pro-inflammatory ingredients that the U.S. consumes in large amounts include trans and saturated fats, omega-6 polyunsaturated fatty acids, sugar, artificial preservatives, artificial sweeteners, refined grains, and alcohol.⁴ 

Saturated fats are usually solid at room temperature and are found in animal fats and tropical oils. They increase LDL levels (the bad cholesterol) and increase your risk of cardiovascular disease. 
Trans fats are formed when liquid oils are hydrogenated, which helps keep processed foods such as margarine, shortening, deep-fried foods, fast foods, and commercial baked goods shelf-stable. Trans fats also raise LDL levels and lead to free radical formation, which oxidizes LDL cholesterol and results in inflammation.  

Oxidized LDL contributes to atherosclerosis and blood clots in the arteries by causing dysfunction in the endothelial cells (the inner lining of the veins and arteries). Damaged endothelial cells produce cytokines, which help promote the deposition of fat plaques within the arteries. These can lead to blood clots, which can become clots in the heart or brain and cause strokes.⁵  

Sugar (glucose) is contained in baked goods, flavored yogurts, candies, soft drinks, and fruit juices, among other products. Interestingly, white bread made with highly refined flours is registered by the body as sugar. Higher levels of glucose in the bloodstream lead to an abundance of reactive oxygen species (a type of free radical), which damage DNA as well as activate the production of advanced glycation end products (AGEs - an oxidant formed when sugars chemically react with proteins). AGEs accumulate in the tissues and contribute to the development of diabetic complications. Additionally, AGEs can oxidize LDL cholesterol and lead to microvascular complications through endothelial cell disruption. AGEs that bind to the a specific receptor, RAGE, trigger a pro-inflammatory cascade, which can lead to scavenger cells (macrophages) attacking affected tissues.⁶ 

Free Radicals

Saturated and trans fats, alcohol, smoking, artificial preservatives, and stress contribute to free radical production. When free radicals circulate without opposition from protective antioxidants, the membranes surrounding the mitochondria become more permeable and leak contents into the rest of the cell. When the leak is detected by certain receptors, an inflammatory cascade follows, leading to further cell damage. Free radicals that are linked to oxidative stress and AGEs result in chronic degenerative inflammatory disorders, such as cancer and aging.⁷ 

Advanced Glycation End Products (AGEs)

The advanced glycation end products consumed in the diet also play a role in degenerative diseases. AGEs are most commonly consumed in the form of meats cooked at high temperatures, dairy products, and foods with a high sugar content. AGEs make cells stiffer and dysfunctional by negatively modifying proteins and damaging the molecules the cells secrete that help support neighboring cells. They lead to the oxidation of LDL cholesterol and atherosclerosis. 

AGEs can also contribute to degenerative disorder complications (for example, diabetic nephropathy) by accumulating in the tissues. AGEs also bind to a specific receptor, RAGE, which plays a role in the copying of RNA in the creation of cells and the proteins located on the cell's surface that make the cells stick together, causing atherosclerosis. The binding of AGEs with RAGE is known as AGE-RAGE and also stimulates the movement of scavenger cells to organs throughout the body, leading to damage and dysfunction. AGEs thus play a role in atherosclerosis and heart disease,⁸ diabetic complications,⁹ renal failure, nervous system disorders, and aging.¹⁰ 

Anti-inflammatory Omega-3s vs. Pro-inflammatory Omega-6s

There are 2 essential fatty acids we must obtain from our diet because our bodies cannot synthesize them: alpha-linolenic acid, an omega-3 fatty acid, and linoleic acid, an omega-6 fatty acid.

Both omega-3 and omega-6 fatty acids are stored as phospholipids in the cell membrane and utilize the same enzymes. Because these polyunsaturated fatty acids (PUFAs) are essential, the ratio of omega-3s to omega-6s in the diet will determine which type predominates in the cell membranes and which types of signaling molecules are created by the cell when it is stimulated by inflammatory hormones.¹¹ A high intake of omega-6s, typical in the Western diet, produces mostly harmful inflammatory hormones. These include those responsible for increased activation of new platelets, which also makes those platelets more likely to stick together; and those responsible for inducing fever. By using the enzymes Omega-6s need to produce these harmful hormones, Omega-3s can keep the omega-6s from being utilized: they are considered anti-inflammatory.¹²  

It is important to maintain the recommended 4:1 or 2:1 ratio of omega-3 to omega-6 polyunsaturated fatty acids in the diet, especially because the standard American diet is high in inflammatory omega-6s. Here's how you can improve your ratio of omega-3s to omega-6s:

• Cook with oils that are high in omega-3s such as olive oil, macadamia nut oil, canola oil, or avocado oil. 
• Limit processed, fried, and fast foods. 
• Read food labels carefully since many omega-6s are hidden in packaged foods in the form of corn oil, safflower oil, or hydrogenated oils. 
• Look for low omega-6 content in dressings and sauces.

Pro-inflammatory Fats are found in: Trans fats (hydrogenated oils) Packaged and processed foods (high in omega 6)

Anti-inflammatory Fats are found in: Cold water fish: salmon, tuna, trout Flax seed, chia seed Olive oil Walnuts (high in omega-3 PUFAs and MUFAs)

The Anti-inflammatory Diet is the Mediterranean Diet

The purpose of the Anti-inflammatory diet is to provide proper nourishment for the body that also protects against chronic inflammation. It shares most of its principles with a Mediterranean style diet. 

• Eat a balanced variety of macronutrients.
• Reduce saturated fats.
• Eliminate all foods containing trans fats.
• Eat at least one good source of omega-3 fatty acids every day.
• Eat at least one serving of whole grains at every meal.
• Consume lean sources of protein.
• Move to a predominantly plant-based diet.
• Eliminate processed and refined foods.

The Anti-inflammatory diet is a slight modification of the Mediterranean diet and similarly encourages eating vegetables, legumes, fruits, nuts, whole grains, lean proteins like fish, and good fats such as olive oil. It also emphasizes reducing consumption of full-fat and processed animal meats.¹³ 

Recommendations

1. Remove refined and processed foods from the diet. Do this by cooking at home as much as possible with fresh and nutritious ingredients.

2. Try to meet daily recommended servings of fruits, vegetables, whole grains, healthy fats and proteins a day. Aim for a rainbow colored plate with ample fruits & vegetables.

3. Avoid omega-6 fatty acids and trans fats whenever possible. Instead, utilize monounsaturated and omega-3 polyunsaturated fatty acids that have anti-inflammatory effects. 

5. Be mindful of eating and exercising. Excess body fat itself releases pro-inflammatory cell signaling proteins. Keeping the weight off will naturally decrease the levels of inflammation and stress on the body. 

Pro-inflammatory Foods	Replace with Anti-inflammatory Foods
White rice, pasta, bread	Brown rice and Soba Noodles
Pastries and Donuts	Oatmeal and Nut Butters
Hamburgers and French fries	Black bean burgers and sweet potatoes
Bagged potato chips	Legumes

References

1. Cotran, and Robbins. Pathologic Basis of Disease. Eighth ed. Philadelphia: Saunders Elsever, 2010.

2. Centers for Disease Control and Prevention. FASTSTATS - Leading Causes of Death. cdc.gov. April 8,2015. June 2, 2015. http://www.cdc.gov/NCHS/fastats/Default.htm.

3. I S Young, J V Woodside.  "Antioxidants in health and disease." Journal of Clinical Pathology. 2001;54:176-186.

4. Cannon, Christopher P., and Heidi McIndoo. The Anti-inflammation Diet. New York: Alpha, a Member of Penguin Group (USA), 2014. 

5. Viles-Gonzalez, Juan, Valentin Fuster, Juan J. Badimon.  "Atherothrombosis: A widespread disease with unpredictable and life-threatening consequences." European Heart Journal (2004) 25, 1197-1207. 

6. Semba, Richard D., Emily J. Nicklett, and Luigi Ferrucci.  "Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype." Journal of Gerontology: Medical Sciences. 2010 September, 65A(9): 963-975.

7. Lobo, V. et al.  "Free Radicals, Antioxidants and Functional Foods: Impact on Human Health." Pharmacognosy Reviews 4.8(2010): 118-126. PMC. Web. 16 June 2015.

8. Barnard, Neal D. Nutrition Guide for Clinicians. Washington, DC: PCRM/Physicians Committee for Responsible Medicine, 2009. pgs. 251-261.

9. Kalousova, M., J. Skrha, and T. Zima. Advanced Glycation End-Products and Advanced Oxidation Protein Products in Patients with Diabetes Mellitus. Physiol. Res. 51:597-604, 2002.

10. Semba, Richard D., Emily J. Nicklett, and Luigi Ferrucci.  "Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype." Journal of Gerontology: Medical Sciences. 2010 September, 65A(9): 963-975.

11. Keeren, Kathrin, et al.  "Effect of Different Omega-6/Omega-3 Polyunsaturated Fatty Acid Ratios on the Formation of Monohydroxylated Fatty Acids in THP-1 Derived Macrophages." Biology 2015, 4(2), 314-326. 

12. Murray, Robert K. Harper's Illustrated Biochemistry. New York: Lange Medical /McGraw-Hill, 2006.

13. Salas-Salvado, Jordi MD PHD, Patricia Casas-Agustench BSc, Michelle M Murphy PhD, Patricia Lopez-Uriarte BSc, and Monica Bullo PhD.  "The effect of nuts on inflammation. " Asia Pacific Journal of Clinical Nutrition 2008;17 (SI): 333-336.

Timothy S. Harlan, MD, FACP, CCMS
Dr. Gourmet