Effect of the Anti-Inflammatory Diet in People with Diabetes and Pre-Diabetes: A Randomized Controlled Feeding Study

Heather Zwickey, PhD,a,* Angela Horgan, PhD, RD, LD,b Doug Hanes, PhD,a Heather Schiffke, MATCM,a Annie Moore, MD, MBA Helané Wahbeh, ND, MCR, Julia Jordan, MS, RD, LD, Lila Ojeda, MS, RDN, Martha McMurry, Patricia Elmer, PhD, and Jonathan Q Purnell, MD
2019

Abstract

Introduction

Inflammation underlies a variety of chronic medical conditions, including diabetes. The anti-inflammatory diet, one that excludes foods that may stimulate inflammation and includes foods that reduce inflammation, may improve inflammatory biomarkers in people with diabetes and pre-diabetes.

Study Design

Thirty participants with diabetes or pre-diabetes were randomized (2:1) in a controlled feeding study that compared the anti-inflammatory diet (n=20) to a control diet (n=10) based on the American Diabetes Association recommendations. Diets were matched for protein, carbohydrate, fat, and fiber content as closely as possible. Participants were fed an isocaloric diet for 2 weeks, followed by continued ad libitum feeding in their dietary group assignment for an additional 4 weeks. All meals were prepared by the study team.

Outcomes

Primary outcomes included inflammatory markers, including cytokines and hsCRP. Secondary outcomes included body weight and biomarkers for cardiovascular disease and diabetes.

Results

Both diets resulted in trends in reduced markers of inflammation, especially with weight loss. In addition, glucose, lipids, and triglycerides all trended downward, also non-significantly and equally in both groups.

Conclusion

Dietary change can improve inflammation as well as other cardiometabolic risk factors. In this study, the anti-inflammatory diet did not affect markers of inflammation more than the control diet.

INTRODUCTION

It is becoming increasingly clear that there is a strong relationship between inflammation and obesity.1–4 One mechanism of this relationship involves adipokines and cytokines.1 Obese people have increased subcutaneous adipocytes (fat cells) that produce chronically elevated levels of leptin.5Higher leptin secretion has been linked with increased production of pro-inflammatory cytokines Tumor Necrosis Factor alpha (TN0046α), Interleukin 1 beta (IL-1β), and Interleukin 6 (IL-6).3 Increased levels of these cytokines and high-sensitivity C-reactive protein (hs-CRP) reflecting longstanding immune activation has been implicated in the pathogenesis of insulin resistance and chronic diseases such as type 2 diabetes.6–8 This suggests that inflammation accompanying obesity may play a role in diabetogenesis, and reducing systemic inflammation is often cited as a benefit of weight loss interventions.9

Diet may also (and independently) affect cytokine levels and inflammation.2 For example, the Mediterranean Diet has been shown to decrease inflammatory cytokines in many conditions.10 In contrast, high trans-fat diets and diets containing sugar-added foods and beverages have been shown to increase pro-inflammatory cytokines IL-6 and TNFα.11,12 Wheat can cause non-celiac gluten sensitivity, a hypersensitivity reaction that leads to production of IL-1β, IL-6, TNFα, and IFNγ.13 In contrast, fish oils containing omega-3 fatty acids decrease inflammatory cytokines IL-6 and TNFα.14Further, anthocyanins in blueberry and blackberry extract have been shown to reduce inflammatory cytokines induced by a high-fat diet.15

Despite supportive data linking diet with inflammation in several chronic diseases, diet complexity, inter-individual variability, and meals consumed as a mixture of foods rather than as isolated ingredients make it difficult to investigate the mechanisms by which an individual dietary component exerts its pro- or anti-inflammatory effects. In addition, it has been proposed that foods influence inflammation indirectly via the gastrointestinal microbiota leading to a specific inflammatory profile16,17 and (or) changes in gut permeability due to hypersensitivity responses to different foods affecting the cytokine production.17,18 The most common of these foods are citrus and nightshade vegetables, which are thought to generate sensitivities in large proportions of the population.19,20 Several diet-associated antigens have also been identified, although the mechanisms by which they exert their effects on the immune system have not been well-elucidated.

A variety of “anti-inflammatory” diets (also known as the hypoallergenic diet, elimination diet, and oligoantigenic diet) have been used in naturopathic medicine for the treatment of many diseases including allergies, irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus.21–23 Despite its therapeutic use, reduction in inflammation has not specifically been demonstrated with this diet.

Anti-inflammatory diets differ primarily in the recommendations regarding which foods should be excluded and included. The varying opinions amongst physicians makes it difficult to study. Nevertheless, all versions of the anti-inflammatory diet include advice regarding inclusion of fats and oils high in polyunsaturated fatty acids, particularly omega-3 fatty acids (fish, canola, flax seed, sunflower, etc.).24,25 In addition, limiting refined carbohydrates (white sugar, brown sugar, and honey) and emphasizing increased intake of seeds and nuts are also cornerstones of the anti-inflammatory diet, making it a low glycemic-index and glycemic-load diet. Reducing glycemic fluctuations is intended to decrease end-organ cellular oxidative stress, reactive oxygen species production, cytokine levels, and other markers of inflammation.26–28

This randomized controlled-feeding study addressed the question of whether the anti-inflammatory diet reduces levels of inflammatory cytokines, parameters of glucose metabolism, and cardiovascular risk factors in patients with pre-diabetes and type 2 diabetes. Participants were chosen for study because these conditions are associated with increased central obesity and levels of inflammatory markers that put them at risk for chronic diseases and poor health outcomes.2,29 We hypothesized that the anti-inflammatory diet would reduce inflammatory markers compared to a control diet, leading to greater improvements in glucose regulation and decreased serum lipid levels.

CONCLUSION

This study demonstrated that for patients with prediabetes and diabetes, both an anti-inflammatory diet and a control diet based on recommendations from the American Diabetes Association showed modest improvements in body weight and trends in benefits for inflammation and biomarkers associated with cardiovascular disease and diabetes. However, we are not able to find a specific benefit of eliminating foods that have commonly been linked with inflammation. In addition, our data suggest that any benefits in inflammation could be the result of the weight loss rather than the specific elimination of inflammatory foods and/or inclusion of anti-inflammatory fats. As a pilot and feasibility study, these conclusions should be considered preliminary and limited in generalizability until a larger trial is conducted.