Anti-Inflammatory Diets

Function

Dietary modifications are one of many interventions that help reduce systemic inflammation. Colloquially, the word "diet" has been reduced to mean calorie restriction or superfood(s) that facilitates significant weight loss in a short amount of time. Within the context of this activity, however, the word "diet" encompasses lifestyle modifications that are implemented as long-term changes for overall health management.

Anti-inflammatory diets are not new constructions; their foundations have existed for centuries. However, anti-inflammatory diets are a relatively new disease treatment and prevention tool. Examples of anti-inflammatory diets include a traditional Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and traditional Okinawan, Nordic, or Mexican diets. These diets share similar core foundations and recommendations. They are components of a holistic lifestyle approach that includes regular physical activity, socialization, adequate rest, and a consumable diet that is biodiverse, fresh, seasonal, and local to the region. These diets' most significant food components are fruits and vegetables, with recommendations for 1 or 2 servings of each at every meal. Whole grains and unsaturated fats, like olive oil, are also heavily emphasized in these diets. Protein is sourced from legumes and lean proteins such as fish and chicken. Red meat is consumed rarely, perhaps once every 1 to 2 weeks. The remainder of dietary caloric intake is from smaller amounts of dairy, alcohol, and processed foods.[1] These diets do not stimulate the inflammatory cascade to a significant degree.

Contrarily, proinflammatory diets stimulate the inflammatory cascade and produce heightened levels of circulating inflammatory markers such as cytokines, chemokines, and PGE2.[7] Proinflammatory diets typically consist of high amounts of processed meats, high-fat dairy products, foods comprising refined sugars and artificial sweeteners, and animal fats such as saturated fats and omega-6 fatty acids.[7] An example of a proinflammatory diet is the Western Diet, which includes all of these components and a culture of overeating and frequent snacking. Western diets also lack vital nutrients, such as vitamins and minerals, and contain food additives, like emulsifiers and sweeteners, contributing to the overall chronic inflammatory state. Emulsifiers are commonly found in fat-based foods and impair the function of the innate immunity of the gut barrier.[8]

Consuming the high amounts of refined grain and sugar products typical of a proinflammatory diet increases the total delivered glucose load, which leads to a compensatory increase in insulin production.[8] Insulin is a proinflammatory hormone; chronic hyperinsulinemia increases the risk of developing metabolic syndrome.[8] Proinflammatory diets are high in sodium and low in potassium due to the increased intake of table salt and processed foods containing added salt and reduced daily potassium-rich foods like fruits and vegetables.[8] This inversion of potassium and sodium concentrations contributes to the development and progression of diseases such as hypertension, stroke, kidney stones, and gastrointestinal cancers.[8] 

Additionally, proinflammatory diets yield a diet-dependent net acid load, known as the estimated net endogenous acid production.[9] After digestion and absorption, all foodstuffs release either an acid or base, usually bicarbonate.[8] Sodium chloride, the salt found in large quantities in proinflammatory diets, increases the diet-dependent net acid load and contributes to the sustainment of chronic, low-grade, pathogenic metabolic acidosis.[8] In contrast, the legumes recommended as a component of most anti-inflammatory diets yield near-zero net acid values.[8] The lower diet-dependent net acid load of anti-inflammatory diets is considered beneficial.

Not all dietary patterns are strictly pro- or anti-inflammatory. Classifying a particular dietary pattern can be facilitated by employing the Empirical Dietary Inflammatory Index (EDII) to generate a dietary score. The EDII is the sum of 9 anti-inflammatory food "groups" and 9 proinflammatory food "groups." [10] The EDII is built on food "groups" rather than nutrients to approximate how people perceive diet.[10] The 9 anti-inflammatory food groups comprise beer, wine, tea, coffee, fruit juices, pizza, snacks, leafy green vegetables, and dark yellow vegetables such as carrots, yellow squash, yams, or sweet potatoes.[10] The 9 proinflammatory food groups include refined grains, high- and low-energy beverages, tomatoes, seafood other than dark-meat fish, vegetables that are not leafy greens or dark yellow, and processed, organ, and red meats.[10] The EDII is designed to assess the dietary quality of a whole diet based on its inflammatory potential. The EDII has proven a reliable predictor of the concentrations of circulating inflammatory markers interleukin 6 (IL-6), C-reactive protein (CRP), adiponectin, and soluble tumor necrosis factor alpha receptor-2 (TNFαR2).[10] The EDII may be employed when initially assessing the inflammatory contribution of a patient's current diet and as dietary changes are implemented over time.

Leading anti-inflammatory diets contain increased proportions of fruits and vegetables. The positive impact of a diet rich in fruits and vegetables, leading to an overall reduction in morbidity and mortality in various cancers, has been widely published.[11][12][13][14][15] Fruits and vegetables contain substances shown to be protective against cancer development, such as allium compounds, selenium, isoflavones, protease inhibitors, phytosterols, and folic acid. These bioactive compounds work collaboratively to exert their protective effects. Selenium, found in Brazil nuts, seafood, and organ meats, is located at the active site of many enzymes that catalyze the oxidation-reduction reactions that may encourage cancerous cells to enter apoptosis.[11] Additionally, selenium inhibits prostaglandin formation and encourages the production of natural killer cells, the specialized leukocytes that destroy infected and cancerous cell populations.[11]

Many anti-inflammatory diets also emphasize the consumption of whole grains (1 to 2 servings per meal), nuts (1 to 2 servings per day), and legumes (1 to 2 servings per week).[16] These foods promote a reduced glycemic index burden. A reduced glycemic index burden has been positively associated with a reduction in inflammation, leading to a reduction in the development of malignancies.[8][1] The increased consumption of whole grains and the reduced intake of refined sugars result in a lower total delivered glucose load and reduced insulin production. Insulin, insulin-like growth factor-1 (IGF-1), estrogens, and androgens are powerful cellular mitogens linked with the development and growth of several tumors.[1]

Long-term adherence to an anti-inflammatory diet contributes to an overall risk reduction for the development of cardiovascular disease. Anti-inflammatory diets, most prominently the Mediterranean diet, promote the preferential consumption of unsaturated fats, such as peanuts, avocados, and fish, over foodstuffs with higher levels of saturated and trans fats, such as cured meats, red meat, and butter. Higher concentrations of unsaturated fats reduce total and low-density cholesterol levels, and lower cholesterol levels are linked to a lower cardiovascular disease risk. Another component of anti-inflammatory diets that assists with improving the lipid profile is phytosterols. Phytosterols found in pistachios, avocados, broccoli, and oranges exert their positive effects by limiting the intestinal absorption of dietary cholesterols.[17] 

Anti-inflammatory diets also reduce cardiovascular disease risk by providing polyphenols in significant concentrations in blueberries, strawberries, apples, dark chocolate, and hazelnuts.[18] Polyphenols inhibit phospholipase A2, cyclooxygenase, and lipoxygenase, reducing prostaglandin and leukotriene production and decreasing prolonged inflammatory states.[19] Due to these effects, many dietary patterns to promote heart health and reduce cardiovascular risk include fruits, berries, and nuts.

Cancer is a group of diseases characterized by the dysregulation of cellular proliferation, a process normally regulated by proto-oncogenes and tumor suppressor genes.[12] Modern cancer therapies sometimes target genomic manipulation to prevent or reverse neoplastic growth. Epigenetics refers to reversible, heritable changes in gene expression in the absence of mutation. Examples of stimuli that can cause epigenetic changes include physical activity, tobacco, alcohol, and diet. Epigenetic modifications occur through DNA and histone methylation, histone acetylation, and noncoding RNA.

The polyphenolic compounds found in peanuts, grapes, and olive oil have been associated with changes in the DNA methylation of genes linked with cancer, specifically tumor suppressors and promoters.[20] Anthocyanins, pigments found in berries, pomegranates, and cruciferous vegetables, were shown to impact the cell cycle by stimulating DNA repair mechanisms through epigenetic modifications.[12] Fisetin is a flavonoid in apples, cucumbers, strawberries, and onions, which has been reported to prevent cancer cell growth.[21] Flavonoids exert anti-inflammatory effects via multiple mechanisms, including inhibiting regulatory enzymes and transcription factors that control inflammatory mediators; they also have potent antioxidant properties, capable of scavenging free radicals to reduce their harmful effects.[3] All of these food products are at the core of various anti-inflammatory diets.

The longer a person lives, the greater the risk of developing a non-communicable disease.[1] Some age-associated neurodegenerative diseases are Alzheimer disease and Parkinson disease, as well as other forms of neurocognitive decline that range from mild cognitive impairment to dementia. Studies evaluating the efficacy of various therapies to delay symptoms onset indicate that therapies initiated earlier in life and sustained, such as an anti-inflammatory diet, promote an overall reduction in disease development and progression.[1][22][23] Several dietary components and supplements have been studied to elucidate those with the most significant impact on cognitive faculties and function. Studied supplements include beta-carotene, folic acid, omega-3 fatty acids, minerals, polyphenols, curcuminoids, garlic, caffeine, and vitamins B12, B6, D, E, and C.[1] A negative or mixed effect on cognitive decline prevention was identified when these supplements were administered as individual dietary components; when integrated into a whole diet, significant protective effects for cognitive deterioration have been identified.[1] These studies emphasize the importance of a whole-diet approach to achieve a significant risk reduction rate for disease development, with early initiation further reducing risk.

Issues of Concern

Anti-inflammatory diets provide significant risk reduction for the development and progression of chronic, noncommunicable diseases. Many disparities and barriers exist to adopting and adhering to an anti-inflammatory diet, including access to and the expense of the healthy foodstuffs comprising most anti-inflammatory diets. When surveyed, consumers reported that they often selected foods based on cost, along with taste and convenience.[24] 

Low-income households repeatedly attributed economic burden as a barrier to initiating a healthier diet.[24][25][26] Low-income households purchase nutrient-dense foods, such as fruits, vegetables, and lean meats, less frequently due to the perceived high cost.[27] Implementing a healthy diet into a household, particularly one that includes children, presents added challenges. Calorie-dense foods such as processed meats, cereals, and pre-packaged, boxed, or ready-to-eat meals contain more fats and sugars but are usually less expensive than nutrient-dense foods.[24] Calorie-dense foods are frequently easier to prepare, satisfy hunger more quickly, and may be more palatable to young children, adding to the purchase appeal.[24] Households where adolescents and adults work long hours, often at multiple jobs, have limited time to purchase food and prepare meals.[24] Residents of many lower-income communities are affected by food insecurity and frequently live in food deserts characterized by limited access to grocery stores or fresh food; the time required to access healthy foods, often using unreliable or limited transportation methods, adds to overall food costs.[25][26] These factors pose significant challenges for patients to initiate a healthier diet and must be accounted for by healthcare providers when recommending this treatment and intervention.

Clinical Significance

Dietary modifications focusing on anti-inflammatory bioactive components significantly reduce cardiovascular disease morbidity and mortality risk.[18][1][28] A primary prevention trial comparing overall cardiovascular risk between participants adhering to a Mediterranean diet versus a reduced-fat diet identified a decrease in major cardiovascular events in 30% of participants with a high cardiovascular risk on the anti-inflammatory regimen.[29] Another study focusing on secondary presentation of coronary heart disease noted a 73% relative risk reduction in patients adhering to the Mediterranean diet.[30] These findings suggest that adherence to a typical anti-inflammatory diet reduces coronary vessel inflammation and the overall risk of CHD development.[30]

Evidence supports a significant impact on developing breast and colorectal malignancies with strict adherence to an anti-inflammatory diet, specifically the Mediterranean diet.[15][31][32] The effect of diet is further emphasized on the development of colorectal cancer by data that indicates reduced adherence to a proinflammatory Western diet reduces the incidence of malignancy.[32] A higher adherence to the Mediterranean diet demonstrated a lower incidence of prostate cancer and reduced aggressivity of the disease.[13] For head and neck cancers, moderate adherence to the Mediterranean diet has been connected to a risk reduction of 17%, while high adherence showed a reduction of 34%.[14]

Higher adherence to anti-inflammatory diets, specifically the Mediterranean diet, is associated with a significant reduction in the incidence of Alzheimer disease.[33] Similar findings are noted when examining the potential relationship between cognitive decline and the incidence of dementia and adherence to a Mediterranean lifestyle of exercise, diet, and social engagement; adherence to a Mediterranean lifestyle demonstrated a 72% risk reduction for the development of dementia in those with the highest level of adherence.[34] The lifestyle of the origin countries of the Mediterranean diet, including Greece, Italy, Spain, Egypt, and Lebanon, includes social engagement, physical activity, adequate rest, and culinary activities, which provide many positive neurocognitive benefits when combined with the dietary pattern. The PREDIMED study demonstrated a benefit in cognitive function with higher levels of Mediterranean diet adherence over 4 to 6 years, specifically in global cognition, memory, and executive function, compared to those with only 6 months of adherence[23].

Clinicians in various specialties can use these findings to support recommending dietary changes to improve overall health status. Incorporating an anti-inflammatory diet with lifestyle modifications and medical therapies can provide long-term risk reduction of chronic, noncommunicable disease processes such as cardiovascular disease, malignancies, and neurocognitive decline.

Enhancing Healthcare Team Outcomes

Evidence has consistently demonstrated that adherence to a healthy diet reduces overall morbidity and mortality and the risk of cardiovascular disease and certain malignancies.[1][18][23] Long-term adherence to an anti-inflammatory diet requires a paradigm shift for patients, from expecting readily observable changes in a short timeframe to making lifestyle modifications for sustainment or improvement of current health status over their lifetime. Several factors are associated with better patient adherence to lifestyle modifications.[35] Behavioral habits, including current dietary habits, high levels of physical activity, and self-monitoring of health statistics, play a role in successful adherence. Cognitive components such as reduced disinhibition and confidence in achieving personal goals, personality traits like resiliency, and buy-in and support from family members all promote adherence to lifestyle modifications.[35] 

Comprehensive programs facilitated by multidisciplinary, interprofessional teams that combine dietary recommendations with specific cognitive and behavioral strategies result in greater long-term patient adherence to lifestyle modifications.[35] A lifestyle modification team may include but is not limited to, physicians, advanced practice providers, dieticians, nutritionists, psychologists, clinical nursing staff, and trained lifestyle counselors.[35]. This interprofessional team can create individualized plans tailored to disease prevention, symptom management, current lifestyle, and access to necessary resources, providing the patient with personalized, comprehensive, supportive care to improve long-term outcomes.

The increasing average life expectancy of the general population also requires a paradigm shift for providers, expanding our focus on increasing the quality of these extended years by reducing the burden of chronic disease. Working with patients to implement an anti-inflammatory diet can help accomplish this goal. Each recommended anti-inflammatory diet, implemented individually or in combination, exhibited long-term, positive effects on chronic diseases such as cardiovascular disease, cancer, and neurocognitive decline. The overall risk reduction afforded by adherence to these diets comes from a synergistic combination of protective bioactive components in high quantities within these anti-inflammatory diets. To achieve the overall risk reduction and positive health effects of these anti-inflammatory diets, they should be incorporated as a lifestyle modification with a mindset of long-term sustainability. By integrating these anti-inflammatory diets, the goal of a life with both quality and quantity is achievable.