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Tuesday, 4 December 2018

Integrative Medicine Chapter 88 - Antiinflammatory Diet

Integrative Medicine (Fourth Edition) 2018, Pages 869-877.e4 Author links open overlay panelWendyKohatsuMDScottKarpowiczMD https://doi.org/10.1016/B978-0-323-35868-2.00088-8 Get rights and content Previous chapter in book Next chapter in book Introduction The rate of chronic disease related to poor diet has risen to staggering proportions in the United States. A recent large meta-analysis indicates dietary factors are currently the leading risk factor for death and disability in the United States, responsible for more than 700,000 deaths and almost 15% of disability-adjusted life years in 2010.1 These diseases—including cardiovascular disease, diabetes, asthma, metabolic syndrome, depression, arthritis, and others—are characterized by a state of chronic, low-grade inflammation.2 Medications—nonsteroidal antiinflammatory drugs (NSAIDs), statins, and biological agents—certainly can be used to reduce inflammation;3 however, we must also help patients tackle the root causes of chronic inflammation created and perpetuated by a lifetime of unhealthy lifestyle habits. A large and growing body of evidence indicates that dietary modifications can have a significant impact on this chronic, low-grade inflammatory state.4, 5 Americans consume 5.5 pounds of food per day.6 We can take a more proactive, preventative approach by investing our 5+ pounds of daily food in healthy choices that decrease inflammation and thus chronic disease. To promote health and mitigate inflammation, integrative physicians must promote lifestyle changes and learn to use food as medicine. This chapter provides the most recent data to help integrative physicians tailor an antiinflammatory diet that is effective, acceptable, and delicious to each patient. Mechanisms and Measurement of Inflammation Several mechanisms by which food influences inflammation have been studied: • Modulation of eicosanoid activity. For example, compounds in culinary spices such as turmeric suppress cyclooxygenase-2 (COX-2) expression and in nutmeg, inhibit tumor necrosis factor (TNF)-alpha release in animal studies.7 • Pro- and antioxidant effects. Increased antioxidant food intake is correlated with lower C-reactive protein (CRP) levels8 and with a lower incidence of joint inflammation.9 • Insulin and glucose levels. A high dietary glycemic load was associated with elevated CRP concentrations,10 and elevation in inflammatory markers has been shown to precede type 2 diabetes11 (see Chapter 87). • Genetic and intracellular expression. A Mediterranean diet12 and omega-3 fats have been shown to modulate gene expression related to inflammation.13 • Modulation of endothelial function. Mediterranean diets powerfully affect endothelial markers.14 • Gastrointestinal dysbiosis. Numerous recent studies support that disruption to the gut microbiome can trigger a host of diverse inflammatory diseases.15, 16, 17 The gut microbiome may indeed be the frontier on which the battle of dietary inflammation is initially fought. Measuring Inflammation Current medical practice is better at diagnosing the multitude of illnesses caused by inflammation than catching it early in the disease process. Having validated ways to measure inflammation can enable us to intervene more proactively. CRP is a commonly used biomarker of inflammation, and CRP levels are elevated with both chronic disease and as an acute-phase reactant. High-sensitivity CRP (hs-CRP) is a more sensitive measure to assess basal levels of CRP at the lower range of 0.20–10.0 mg/L; an hs-CRP > 2.0 may signal higher cardiovascular risk.18 Other markers, such as TNF-alpha, interleukin-6 (IL-6), IL-1 beta, adhesion molecules, and endothelial function tests are used more widely in research to measure inflammation and are starting to emerge for clinical use. Recent studies have examined our food and its relationship with these inflammatory markers directly. A new dietary inflammatory index (DII)2 has been developed to assess the inflammatory potential of various diets, and a Mediterranean diet score is already in use.19 We anticipate that these tools will be useful for counseling patients on therapeutic diets in the future. The Mediterranean Diet Is an Archetype of an Antiinflammatory Diet The antiinflammatory diet is not one specific diet—indeed, there are many different diets that possess antiinflammatory effects. That being said, the Mediterranean diet is perhaps the most well-researched example of an antiinflammatory diet and serves as an archetypal model to further explore features of an antiinflammatory diet. Multiple studies and a recent meta-analysis have demonstrated the antiinflammatory effects of the Mediterranean diet as measured by serum inflammatory markers and measures of endothelial function.20, 21, 22 The importance of this diet is further underscored by the large and growing body of evidence from both epidemiological studies and randomized controlled trials that demonstrate a significant mortality benefit and reduction in chronic disease with adherence to the Mediterranean diet.19, 24, 25, 26 The Mediterranean diet is rich in vegetables, fruits, and whole grains; emphasizes nuts and olive oil as sources of fat; and gives preference to legumes, lean poultry, and fish rather than red meat (Fig. 88.1 and Table 88.1). Sodas, sweets, and refined baked goods; processed meats; and butter or similar spreadable fats are discouraged. Wine in moderation is an important component of the diet for those who choose to drink alcohol. This diet thus stands in stark contrast to the standard American diet, with its heavy intake of refined carbohydrates, red meat, added sugars, and limited portions of green vegetables, fruits, and whole grains. Download full-size image FIG. 88.1. The Mediterranean diet pyramid. TABLE 88.1. Original Mediterranean Diet Score19 Give yourself 1 point for each “yes” answer and 0 for each “no” Dietary Component YES NO Vegetables: 4 or more servings a day Legumes: 1 or more servings a week Fruit: 3 or more servings a day Nuts and seeds: 1 or more servings a week Whole grains: 1 or more servings a day Fish: 4 or more servings a week Fats: More unsaturated fats, such as olive oil, than saturated fats, such as butter Alcohol: 1/2 to 1 drink a day for women; 1 to 2 for men Red and processed meat: Fewer than 2 servings a day for women, fewer than 3 a day for men TOTAL: Totals of 6 or higher put you in the range of highest benefit. Scores less than 4 mean you are getting little or no protection. It is important to note that the Mediterranean diet is a pattern of eating, not a collection of specific recipes. Thus, while the traditional Mediterranean diet finds its origin in the Mediterranean region, the dietary pattern itself is broadly applicable across other regions, cultures, and food traditions. Multiple studies have demonstrated significant benefits of the Mediterranean diet when taken out of its traditional cultural context, including studies on Nordic,27 Polish,28 Indian,29 and Okinawan30 diets that follow the overall Mediterranean dietary pattern. Thus, patients whose individual food preferences may not match those of the Mediterranean region should have little difficulty adapting it successfully to their own taste preferences. It is also cost-effective.31, 32 While it is useful to explore in more detail the individual components of the Mediterranean diet, it is also important to note that the overall benefit of the Mediterranean diet is likely a result of the diet as a whole rather than any specific component. For example, in one of the most important epidemiological studies on the Mediterranean diet, the authors demonstrate that while an increase in a single component of the Mediterranean diet did not result in a significant benefit, an increase in any two components resulted in a statistically significant 25% reduction in overall mortality.19 Furthermore, data indicate that even relatively small changes can have important health impacts. The PREDIMED trial, a recent large randomized controlled trial assessing the impact of the Mediterranean diet on cardiovascular disease, showed that patients who were more adherent to the Mediterranean diet by just two of the component items significantly reduced their rate of cardiovascular disease and its associated mortality.23 Components of an Antiinflammatory Diet Fats Famous for their taste and palatability, antiinflammatory diets, especially the traditional Mediterranean diet, are characterized by their typically higher percentage of calories from fat—usually in the 40%–50% range—which adds both high satiety and flavor. Choosing the right fats—both the quantity as well as the quality—is important for reaping the key benefits of an antiinflammatory diet (Table 88.2). TABLE 88.2. The Skinny on Fats Type Subtype Metabolite Food Sources Notes Saturated Long chain TG Animal fats—meat, butter, cheese Amount in the diet is controversial, 7%–10% of calories. MCT SCT Tropical oils—coconut, palm Shorter-chain saturated fats may burn in the body more like carbohydrates. Monounsaturated Olive oil Nuts Avocados Peanuts Higher EVOO intake associated with a reduction in the CVD mortality by half.55 Reduces LDL and increases HDL. Polyunsaturated Omega-6 Essential fatty acid AA GLA Corn oil Most vegetable oils Soya Omega-6 fatty acids are essential fatty acids easily obtainable in the diet; however, usually in gross excess of omega-3s. Omega-3 Essential fatty acid ALA Flax, hemp, chia, walnuts ALA conversion to biologically active EPA and DHA is only about 10%–15%. EPA DHA Cold water fish (e.g., salmon), algae Potent antiinflammatory effects. Eat 2+ fatty fish servings/week.162 AA, arachidonic acid; ALA, alpha linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; GLA, gamma linoleic acid, an antiinflammatory omega-6; MCT, medium-chain TG; SCT, short-chain TG; TG, triglyceride. a Soy contains both omega-6 (54%) and omega-3 (7%) fatty acids. There is a lot of controversy on the amounts of fats in a healthy diet. On one end of the spectrum, the Japanese diet contains only about 7% of its calories from fat, while a Mediterranean diet about 45%. For all types of fats, it is critical to pay attention to the quality, not just quantity. Choosing fresh, natural, organic, unrefined oils and fats will ensure protection against rancidity, oxidation, nutrient degradation, and contamination. The two essential fatty acids—omega-6 and omega-3—need to obtained from the diet as they cannot be synthesized by the body. In general, omega-6 fats lead to more inflammation, and omega-3 metabolism leads to the formation of less-inflammatory or antiinflammatory prostaglandins and leukotrienes. Thus, it is critical to keep a healthy balance between the two. A truly free-range egg has a favorably low omega-6:omega-3 ratio of only 1.3 compared to a conventionally raised egg with a ratio of 19.4.35 A few dietary fat dilemmas are as follows: 1. Omega-6 fats are vastly more abundant in the Western diet (usually 15–20×) compared with omega-3s. A ratio of 1:1–4:1 of omega-6 to omega-3 is recommended.36, 37 This means that Americans need to cut down on excessive intake of omega-6 fats and ramp up consumption of omega-3s (Fig. 88.2). Download full-size image FIG. 88.2. Influence of omega-6 and omega-3 fatty acids on inflammation. 2. Omega-3 and -6 fats compete for the same metabolic enzymes, so high levels of omega-6 fats may suppress the already limited metabolism of omega-3 fats. At low levels of omega-3 intake, omega-6 fats are associated with the highest amount of inflammation.38 3. Renewable, plant-based forms of omega-3 fats largely contain alpha-linolenic acid (ALA) rather than eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The body needs to metabolize this ALA into EPA and DHA to exert its antiinflammatory effects, though it is able to do so in only relatively low amounts—only about 10%–15% of ALA is metabolized into EPA and then subsequently into DHA. Cold-water fatty fish, on the other hand, naturally contain higher amounts of preformed EPA and DHA, which exert antiinflammatory effects without the need for further metabolism. However, for environmental, heavy metal contamination, and cost issues, fish consumption is often limited. 4. Fish oil supplements do not seem to yield the same omega-3 benefits as eating fish itself.39, 40 Dose, quality, and human genetic variation may explain these differences.41 Remember the acronym S.M.A.S.H. for your best sources of omega-3 EPA and DHA in cold-water fish such as Salmon (wild Pacific), Mackerel (Spanish), Anchovies, Sardines, and Herring. The Evil of Trans-Fatty Acids When a naturally liquid polyunsaturated fat is chemically converted via hydrogenation to a more solid fat, synthetic trans-fats are formed (Fig. 88.3). While more shelf-stable, these trans-fats (also known as hydrogenated fats, or partially hydrogenated fats) wreak havoc on the body, disrupting the native cis-alignment of membrane fats,42 increasing serum levels of lipoprotein(a) and triglycerides,43 as well as inflammatory mediators. In June 2015, the U.S. Food and Drug Administration (FDA) finally declared that partially hydrogenated oils are not “generally regarded as safe” (GRAS) in human food. Manufacturers have 3 years to remove partially hydrogenated oils from their products. Download full-size image FIG. 88.3. Hydrogenation of polyunsaturated fat. Olive Oil Olive oil is a key component of the traditional Mediterranean diet and a growing body of evidence supports its inclusion as an important part of an antiinflammatory diet.14 Olive oil is rich in oleic acid, a monounsaturated fatty acid. Additionally, virgin and extra virgin olive oils, unrefined versions made by pressing freshly picked olives, have high quantities of polyphenols, which have potent antioxidative properties.45, 46 The benefits of olive oil likely derive from a synergistic relationship between these key components.47 Growing evidence from intervention-based trials indicates that olive oil reduces key cardiovascular risk factors. Olive oil, particularly the high-polyphenol virgin or extra virgin varieties, improves lipid profiles and reduces dyslipidemia through an improvement in the quantity and function of high-density lipoprotein (HDL) cholesterol and reduction in low-density lipoprotein (LDL) cholesterol.23, 48, 49 Additionally, olive oil has been shown to decrease blood pressure in patients with hypertension, improve endothelial function in patients with atherosclerotic disease, and reduce markers of inflammation.51, 52 Further evidence suggests that regular olive oil consumption, independent of total energy intake, decreases the risk of new-onset diabetes.53 Importantly, evidence from both epidemiological and intervention studies demonstrate a mortality benefit from olive oil consumption. The recent PREDIMED randomized controlled trial demonstrated a significant reduction in cardiovascular events and cardiovascular disease-related mortality in patients consuming a Mediterranean diet supplemented with extra virgin olive oil.23 Further analysis of these data suggests a 10% reduction in cardiovascular disease for every 10 additional grams of extra virgin olive oil consumed per day.55 These data correspond with multiple epidemiological studies that support a significant inverse correlation between olive oil, particularly the extra virgin variety, and coronary heart disease,56, 57 stroke,58 and cardiovascular mortality.59 Nuts Nuts are a rich source of monounsaturated and polyunsaturated fats, in addition to providing fiber, minerals, and other important nutrients.60, 61 Increased nut consumption has an important effect on reducing serum inflammatory markers, including CRP and IL-6.62 More importantly, multiple recent prospective studies indicate that increased nut consumption decreases metabolic syndrome,63 coronary artery disease,64 and total mortality in addition to cancer-specific and cardiovascular disease-specific mortality.65, 66 These studies support a dose–response relationship, and data from the PREDIMED trial suggest that consuming just three servings of nuts per week can reduce all-cause mortality by 39%.66 Despite slightly different fatty acid compositions and nutritional components, similar benefits are observed across a wide range of tree nuts as well as peanuts.65 Coconut Oil Recently, coconut oil has garnered considerable attention in the lay press as a health food with a myriad of purported health benefits.69 Saturated fat comprises more than 90% of the fat content of coconut oil, the majority of which is in the form of medium-chain fatty acids.70 However, in contrast to the longer-chain saturated fatty acids more typically found in animal fats, medium-chain fatty acids are more easily metabolized.71 Recent data from a human trial suggest that coconut oil, at least in daily doses of 30 mL, may not have the same dyslipidemic properties and proinflammatory properties as other saturated fats.72 In addition, virgin coconut oil contains high concentrations of polyphenols and may therefore have antioxidant as well as antiinflammatory effects, as demonstrated in animal models.73, 74 Nonetheless, there is a dearth of quality evidence from human trials assessing the antiinflammatory or overall health benefits of coconut oil, and additional data are needed before it can be strongly recommended as a component of an antiinflammatory diet. Carbohydrates Whole grains contain naturally occurring fiber, lignans, magnesium, zinc, B vitamins, and vitamin E that may help fight inflammation. Actively replacing refined carbs with whole grains in the diet has been shown to reduce inflammatory markers.75 Prospective studies have shown that higher dietary fiber and whole-grain intake is associated with decreased hs-CRP and IL-6.76, 77, 78 Whole-grain consumption substantially lowers the risk of inflammation-mediated diseases,79 such as cardiovascular disease, diabetes, cancer, and obesity. One study80 of 522 diabetic patients showed that including 15 g of dietary fiber for every 1000 calories consumed daily with lifestyle changes (moderate exercise) significantly reduced CRP by 27%. Perhaps the most important factor that best represents the inflammatory potential of a carbohydrate-containing food is its glycemic load (GL) (see Chapter 87). Excessive consumption of highly processed carbohydrates, e.g., white flour and refined sugars, with high GL, cause abnormal surges in blood glucose and insulin levels, which then overloads mitochondrial capacity thus creating free radicals.81 Immediate increases in CRP and inflammatory cytokines can be seen with a single meal.82 One study found a strong link between high dietary GL and elevated CRP concentrations in women; CRP levels were more than doubled (3.7 mg/L) in the group consuming the highest GL compared to the lowest GL (1.6 mg/L).10 Similarly, higher dietary glycemic index (GI)/GL has been associated with higher levels of TNF-alpha and IL-6.84 Even with the same amount of calories, choosing higher-quality carbohydrates with low GLs can lower the inflammatory profile.85 Not surprisingly, diets rich in unprocessed, natural plant foods such as the Okinawan or Mediterranean diets have lower GLs, substantially lower postprandial glucose levels, and are associated with improved cardiovascular health and longevity.86 Minimally processed low-GL foods—vegetables, fruit, nuts, seeds, and whole grains—do not result in adverse postprandial inflammatory effects, but high-GL foods do.87 Other mechanisms besides GL also likely help explain the benefit of whole grains in an antiinflammatory diet. A distinct benefit of whole-grain intake is supporting a more favorable gut microbiome composition that lowers both gut and systemic inflammation.88, 89, 90 Furthermore, another reason to consume whole grains is that the active phytochemicals are concentrated in bran (fiber) and the germ (carbohydrate); refining wheat with removal of the fiber causes a 200- to 300-fold loss in phytochemicals and increases the speed of sugar absorption (the GI)91 (Fig. 88.4)! Portion control is also important! Overconsumption of even healthy, low-GL foods can trigger a hyperglycemic response and inflammation. Excess calories regardless of source also contribute to obesity, which itself produces inflammation.92 Download full-size image FIG. 88.4. Fiber (bran) helps reduce the speed of sugar (germ) absorption. Vegetables and Fruit Vegetables and fruit—while often classified under the macronutrient “carbohydrate”—deserve their own stand-alone category due to their natural abundance of nutraceutical benefits! Vegetables contain the highest concentrations of vitamins, minerals, and other protective phytochemicals, with a lower caloric density compared with other foods. Rich in biochemical complexity, whole vegetables and fruit are superior to any single isolated nutrient. Citrus fruit, for example, contains not just vitamin C, but some 60 flavonoids, 20 carotenoids, and limonoids. Higher intake of vitamin C from food sources has been associated with lower CRP and tissue plasminogen activator (tPA) levels.93 The inadequate consumption of vegetables and fruit in the United States is appalling. It is estimated that Americans only consume 1.6 servings of vegetables per day and only one fruit per day.94 Fewer than 10% of Americans eat enough fruits and vegetables. Even more concerning is that the largest single contributor to fruit intake was orange juice and that potatoes still dominate vegetable consumption; fried potatoes account for about one-third of the “vegetables” that adolescents consume.95 Studies support that people who consume more vegetables and fruit have lower rates of inflammatory disease such as heart disease, insulin resistance, and some cancers.96, 97, 98, 99 High intake of vegetables and fruits, greater than five servings per day, has a significant inverse dose–response association with inflammatory markers such as CRP, IL-6, and adhesion factors.97, 100, 101 The more vegetables and fruit one eats, the less inflammation. Estimates from the US Department of Agriculture (USDA) flavonoid databases also show an inverse association between high flavonoid intake (from fruit and vegetables) and lower CRP levels.103 Flavonoids are responsible for the deep colors of fruits and vegetables and often are a proxy marker for high nutritional quality. In epidemiological studies, higher fruit and vegetable intake was shown to significantly decrease markers of inflammation in adolescents104 and in adult women.97 Adding fruits and vegetables to the diet, especially those rich in flavonoids, significantly improved microvascular reactivity and lowered CRP values.106 Watch the sugar! The American Heart Association recommends that women consume no more than 100 calories/day as added sugar. This equals 25 g of sugar or about six teaspoons. For men, the limit is 150 calories, 36 g of sugar, or nine teaspoons per day. Read labels, this adds up quickly! To satisfy your sweet tooth, choose fresh fruit in season.107 Proteins A large body of data supports the health benefits of plant-based proteins, and they are a healthy alternative to animal sources of protein.108, 109 Legumes are high in protein as well as fiber, iron, folic acid, and B vitamins. Most legumes are deficient in the essential amino acids methionine and tryptophan, but these are found in sufficient amounts in most grains. Randomized clinical trials indicate that regular consumption of legumes is associated with a reduction in inflammatory markers and an improvement in both lipid profiles and endothelial function.110, 111 Legumes make up a substantial part of a healthy antiinflammatory diet, can be prepared in many tasty ethnic dishes, and provide the majority of protein for a hungry world. Substituting healthy protein sources like legumes for red meat is associated with a lower mortality risk.112 In contrast, diets high in red and processed meats are correlated with increases in inflammatory markers, markers of glucose dysregulation, and dyslipidemia.113, 114, 115 Furthermore, diets higher in red meat, especially in processed forms (e.g., cured meats and sausages, bacon, and processed lunch meats) are associated with higher rates of cardiovascular disease, certain cancers, and all-cause mortality.116, 117, 118 Although it is not entirely clear what component of red meat contributes to its inflammatory effect, several clinical trials suggest that consuming lean meat may not result in the same proinflammatory effect that is observed with the higher fat, more processed red meats typically found in a modern American diet.119, 120, 121 For those who do eat meat, studies support trimming visible fat122 and avoiding charring the food to lessen the inflammatory impact.123 In addition to lean meats, animal protein sources from fish124 and dairy125, 126 are suitable components of an antiinflammatory diet. Fish While a source of high-quality protein and healthy fat, fish often swim in waters contaminated with heavy metals such as mercury, cadmium, lead, and other pollutants such as polychlorinated biphenyls (PCBs). These are proinflammatory and impair metabolic function. Even taking this into consideration, one review127 reports that the health benefits of eating fish exceed the potential risks. Avoid fish highest in methylmercury—shark, swordfish, golden bass (tilefish), and king mackerel. A serving of albacore tuna contains 0.35 ppm methylmercury with 1.0 ppm being the EPA’s “allowable” upper limit/day, so limit it to no more than one serving per week.128 Some of the safest fish are tilapia, anchovies, and wild salmon. Other Antiinflammatory Foods, Spices, and Supplements • Turmeric: Turmeric is the queen of antiinflammatory spices! Multiple studies have assessed the potential benefits of curcumin, the main component of turmeric (Curcuma longa), on a variety of inflammatory conditions. Several recent randomized controlled trials have shown improvements in inflammatory markers and endothelial function with regular administration of curcumin.129, 130, 131 Furthermore, trials have found curcumin equivalent in pain relief to ibuprofen and diclofenac for knee osteoarthritis132 and rheumatoid arthritis,133 respectively. Curcumin has shown promise in other inflammatory conditions, including maintenance of remission in ulcerative colitis134 and improvement in signs and symptoms of oral lichen planus.135 Especially considering its long track record of culinary use and excellent side effect profile in all the trials in which it has been studied, turmeric represents both a safe and effective addition to any antiinflammatory diet. • Wine: While excessive alcohol consumption is clearly linked to excess morbidity and mortality, a large body of epidemiological data suggests that low-to-moderate alcohol consumption is associated with decreased levels of both cardiovascular and all-cause mortality.136, 137, 138, 139 Wine is of particular interest in the antiinflammatory diet as it is rich in polyphenols, which likely exert numerous antioxidative and antiinflammatory effects.140, 141 Randomized trials have demonstrated a reduction in inflammatory markers142 and improvement in lipid profiles143 with regular, moderate consumption of red wine. • Other spices—ginger, chili pepper, oregano, basil, thyme, and rosemary—also possess antiinflammatory properties144, 145 and add flavor to a wide variety of cuisines. • Cocoa: Cocoa and cocoa-rich products such as dark chocolate contain high quantities of flavonoids, as well as fiber and other important nutrients.146 Multiple trials demonstrate a reduction in serum inflammatory markers,147, 148, 149 improvement in lipid profiles,150, 151, 152 and enhanced endothelial function153, 154, 155 with consumption of flavonoid-rich cocoa. Furthermore, a recent trial demonstrated improvement in both walking distance and time in patients with peripheral artery disease after consumption of 40 g daily of dark chocolate.156 Evidence from a meta-analysis of randomized controlled trials indicates a reduction in insulin resistance,157 and epidemiological data suggests a reduction in diabetes incidence with cocoa consumption.158 Mortality data are limited, though one epidemiological study indicated an inverse correlation between chocolate consumption and cardiovascular and all-cause mortality.159 Doses used in trials vary widely from less than 10 g daily to 100 g daily—although the lowest effective dose is not known, 1–2 ounces of dark (at least 70%) chocolate as a tasty and healthy treat is a safe suggestion. Medical Conditions That May Improve With an Antiinflammatory Diet Table 88.3 provides a summary of some of the major diseases for which antiinflammatory diet modifications have shown therapeutic promise. TABLE 88.3. Medical Conditions That May Improve With an Antiinflammatory Diet Arthritis Two randomized controlled trials found turmeric extracts to be as good or better than nonsteroidal antiinflammatory drugs (NSAIDs) at controlling symptoms of knee osteoarthritis132 and rheumatoid arthritis.133 Doses ranged from 500 mg to 1500 mg daily in these trials. Daily administration of a probiotic for 8 weeks was shown in a randomized controlled trial to reduce symptom severity and inflammatory status in patients with rheumatoid arthritis.165 Hypertension Randomized controlled trials found significant reductions in blood pressure in patients who adopted the traditional Mediterranean diet166 and the New Nordic Diet, a Mediterranean diet regional variant.27 Apart from its inclusion in the Mediterranean diet, daily consumption of olive oil results in a clinically significant reduction in blood pressure168—olive oil rich in polyphenols, such as extra virgin olive oil, may be more effective at decreasing blood pressure than regular olive oil.169 Olive oil dosing ranged from 30 mL–60 mL (2–4 tablespoons) daily in these trials. Asthma A recent small trial found improvement in spirometry and quality of life scores in patients with asthma who adopted a Mediterranean diet.170 COPD In one randomized controlled trial, patients with COPD showed significant improvement in lung function [increased forced expiratory volume in 1 second (FEV1)] with greater intake of antioxidant-rich fruits and vegetables.171 Diabetes Data from the PREDIMED trial indicate reduced onset of diabetes with increased adherence to an energy-unrestricted Mediterranean diet.53, 173 In patients with existing diabetes, adherence to an energy-unrestricted Mediterranean diet resulted in a reduction in hemoglobin A1c equivalent to that from mono-drug therapy.174 A low-carbohydrate Mediterranean diet has also been shown to reduce the need for antiglycemic medications in patients with newly diagnosed diabetes.175 Cardiovascular Disease Large randomized controlled trials have demonstrated the Mediterranean diet as an effective means of both primary23 and secondary26, 177 prevention of cardiovascular events, including myocardial infarction and stroke. Supplementation with olive oil55 and nuts66 likely provides even greater benefit. The effect size of dietary change should not be underestimated—secondary prevention trials indicated risk reductions of nearly two-thirds in those adhering to a Mediterranean-style diet. Peripheral Artery Disease The PREDIMED trial suggests that adherence to a Mediterranean diet significantly decreases the rate of new-onset symptomatic peripheral artery disease.181 In a randomized controlled trial of patients with existing peripheral artery disease, daily administration of 40 g of dark chocolate resulted in a significant improvement in walking autonomy.156 Obesity Adherence to a Mediterranean diet was associated with 51% lower odds of being obese and 59% lower odds of central obesity.183 A high amount of olive oil consumption was not associated with higher weight gain or a significantly higher risk of becoming overweight or obese.184 Despite a higher fat content (35% compared to 20%), participants eating a Mediterranean-based diet lost 4.1 kg compared with controls who gained 2.9 kg over 18 months.185 Inflammatory Bowel Disease A randomized controlled trial found that turmeric (Curcumin) at daily doses of 2 g given in conjunction with standard therapy significantly reduced rates of relapse and improved endoscopic and symptom-based disease severity scores.134 A recent case series demonstrated that patients who adhered to a modified antiinflammatory diet showed significant improvement in disease-related symptom scores.187 Nonalcoholic Fatty Liver Disease In adults with nonalcoholic fatty liver disease, data from a randomized controlled trial indicate that patients whose diets are supplemented with olive oil or canola oil at doses up to 20 mg daily showed a reduction in liver span and severity of fatty liver at 6 months.188 A recent meta-analysis found that daily supplementation with omega-3 fatty acids reduced hepatic steatosis.189 Daily doses above 800 mg are effective, although the ideal dose is not yet known. Cancer A recent meta-analysis found that higher adherence to the Mediterranean diet was associated with a 10% reduction in overall cancer incidence and mortality.190 This data indicate the effect may be most pronounced in colorectal and prostate cancer, with reductions in incidence of 14% and 4%, respectively, with increased adherence to the Mediterranean diet. Alzheimer’s Disease and Dementia Adherence to a Mediterranean diet supplemented with olive oil or nuts has been shown to improve cognition and slow age-related cognitive decline.191, 192 In an observational study, higher adherence to a Mediterranean diet was associated with slower cognitive decline as measured by the Mini Mental State Evaluation.193 A recent small pilot study found that daily supplementation with omega-3 fatty acids and alpha lipoic acid (ALA) reduced the progression of cognitive and functional decline in patients with Alzheimer’s disease.194 Doses used in this study were 1.6 g of omega-3 fatty acids and 600 mg of ALA daily. Depression A recent meta-analysis of 19 randomized controlled trials found omega-3 fatty acid supplementation effective in treating patients with both major depressive disorder (MDD) and depressive symptoms without a clear MDD diagnosis.195 Dosing varied widely across trials but averaged 1.4 g of combined EPA and DHA daily. Additionally, another recent trial found that initiating omega-3 supplementation with a selective serotonin reuptake inhibitor (SSRI) resulted in better reduction in depressive symptoms than the SSRI alone.196 Psoriasis In patients being treated for psoriasis, a randomized controlled trial demonstrated that a hypocaloric, omega-3 rich diet significantly reduced symptom severity at 3 and 6 months.197 Conclusion Inflammation is a common pathophysiological mechanism underlying most chronic disease. The antiinflammatory diet is based on evidence-based principles of sound eating to promote health and prevent and reduce inflammation in the body. It is whole food-based nutrition that emphasizes healthy fats, vegetables and fruit, whole grains, legumes, fish, and limited amounts of meat and dairy. It can be recommended as “food as medicine” for a wide variety of common diseases including heart disease, diabetes, obesity, cancer, Alzheimer’s disease, chronic obstructive pulmonary disease (COPD), depression, and gastrointestinal (GI) disorders. Key Web Resources Oldways Preservation Trust. Has the original Mediterranean diet pyramid, and also features culturally inclusive Asian, Latino, and African heritage pyramids. http://oldwayspt.org Anti-Inflammatory Food Pyramid. Dr. Andrew Weil has published a patient-friendly and illustrative antiinflammatory food pyramid. This plan also features berries, Asian mushrooms, soy, tea, and dark chocolate http://www.drweil.com and search for “food pyramid.”119 For data on mercury levels in fish, check out the U.S. Environmental Protection Agency. http://www.fda.gov/food/foodborneillnesscontaminants/metals/ucm115644.htm A good website with healthy Mediterranean-style recipes http://www.eatingwell.com/recipes_menus/collections/healthy_mediterranean_recipes Check out the “Meatless Monday” campaign online. This international movement encourages all to skip meat once a week and explore healthy and tasty vegetarian options. http://www.meatlessmonday.com Download full-size image FIG. 88.5. Patient handout: Antiinflammatory diet. References 1 C.J.L. Murray The state of US health, 1990-2010 JAMA, 310 (2013), p. 591 CrossRefView Record in ScopusGoogle Scholar 2 N. Shivappa, S.E. Steck, T.G. Hurley, et al. 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