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By William C. Haas III, MD, MBA
Assistant Professor, Department of Family and Community Medicine, Arizona Center for Integrative Medicine, University of Arizona, Tucson, AZ
Dr. Haas reports no financial relationships relevant to this field of study.
SYNOPSIS: Stress experienced prior to eating may raise inflammation levels as much as eating a high saturated fat meal in a relaxed state.
SOURCE: Kiecolt-Glaser JK, Fagundes CP, Andridge R, et al. Depression, daily stressors and inflammatory responses to high-fat meals: When stress overrides healthier food choices. Mol Psychiatry 2016; Sept 20. Doi: 10.1038/mp.2016.149 [Epub ahead of print].
The role of inflammation in the development of chronic disease has garnered significant attention among researchers and clinicians. Likewise, the contribution of dietary intake to the inflammatory response has driven new lines of nutritional research and the recent development of “anti-inflammatory” diets. Extensive research supports the benefit of Mediterranean-based anti-inflammatory diets, especially as it relates to reduced inflammation and improved disease outcomes.1,2 However, other lifestyle factors beyond diet contribute to inflammation within the body. Stress and depressed mood both have been linked with increased inflammation.3 When considering diet and mood together, an interesting question arises — does stress affect the inflammatory response of food?
A group of researchers who followed healthy breast cancer survivors attempted to assess the effect of stress as well as depressed mood on the metabolic response to two different high-fat meals. The primary hypothesis maintained that stressors occurring prior to a meal would raise postprandial inflammatory markers. Implied, yet equally important, was the hypothesis that a high saturated fat meal would increase inflammatory markers to a greater extent than a high oleic sunflower oil meal.
Following a double-blind, randomized, crossover study, researchers assigned 38 breast cancer survivors and 20 healthy patients to receive one high saturated fat meal and one high oleic sunflower oil meal at two separate times (approximately 1-4 weeks apart). Patients were excluded from participating if they had a history of cardiopulmonary disease, autoimmune disease, diabetes, or cancer aside from breast cancer. Medications leading to exclusion included lipid-lowering drugs, antihypertensives, and/or any medications with immunological or endocrinological effects.
Both meals incorporated eggs, turkey sausage, and biscuits with gravy for a total of 930 kcal, consisting of 60% fat, 25% carbohydrate, and 15% protein. The fat content for each of the meals varied. The breakdown for the high saturated fat meal was 16.84 grams palmitic acid and 13.5 grams oleic acid (ratio 1.93), while the breakdown for the low saturated fat meal was 8.64 grams palmitic acid and 31.21 grams oleic acid (ratio 0.67). In an effort to standardize the effect of the test meals, participants were instructed to avoid alcohol one day prior to the study and strenuous physical activity two days prior. Additionally, participants were instructed to avoid all perceived anti-inflammatory medications and/or supplements one week prior to the interventions. Before each meal, participants also recorded the number of daily stressors over the previous 24 hours using the Daily Inventory of Stressful Events tool. Depression history was evaluated using DSM-IV criteria, and the Center for Epidemiological Studies Depression Scale assessed depressive symptomatology over the week prior to the interventions.
To evaluate the primary outcome of inflammation, blood samples were drawn before the meals and at 2, 4, and 7 hours after the meals. Samples were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), the latter two representing adhesion molecules known to reflect generalized inflammation and atherosclerotic plaque burden, respectively.4
At baseline, there were no significant differences among the biometric measurements between the control group and breast cancer survivors. The number of prior day stressors were equivalent between the two groups; however, breast cancer survivors were more likely to have a history of major depression. With regard to the primary variables, baseline fasting inflammatory makers were equivalent between the groups with the exception of ICAM-1, which was higher in breast cancer survivors. In the fasting state, there also were no associations noted between prior day stressors and inflammatory markers.
With regard to postprandial responses, the majority of the sampled inflammatory markers (CRP, ICAM-1, VCAM-1) were higher following the saturated fat meal compared to the high oleic sunflower oil meal when no stressors were reported (P = 0.04, 0.02, and 0.05, respectively). Interestingly, when accounting for prior day stressors, postprandial inflammatory markers rose significantly after the high oleic sunflower oil meal, but not after the high saturated fat meal. In fact, for each additional prior day stressor reported, CRP increased by 2.9% after the high oleic oil meal. There were no significant effects of depression history on inflammatory markers (P > 0.07 for all tests).
The effect of food and stress on inflammation has received significant attention because of their direct effects on health and well-being. The present study is one of the first to evaluate the ability of stress to modulate the inflammatory response of different food. Somewhat unexpectedly, the researchers found that prior stress exposure negated differences in inflammation resulting from a high saturated fat or a high oleic fat meal. In essence, consuming a meal with healthy fat while under stress resulted in the same amount of inflammation as an unhealthy fat-based meal. Equally intriguing was the finding that stress exposure did not further increase inflammation levels after consuming a saturated fatty meal. Unfortunately, the researchers were unable to account for why stress did not further increase inflammation levels after high saturated fat intake.
When interpreting the results of the study, some attention must be directed toward the composition of the test meals. The caloric makeup of the low saturated fat meal consisted predominately of high oleic sunflower oil, an oil designed to be lower in omega-6 fatty acids and higher in monounsaturated fats compared to traditional sunflower oils. Regardless of the different fat sources, it would be a stretch to call either meal healthy. Although anti-inflammatory diets emphasize the incorporation of healthy fats, a number of other aspects contribute to their health-promoting properties. Unfortunately, the meal with a perceived healthy fat content still contained highly refined carbohydrates with little fiber and no plant-based phytonutrients. It is unclear whether inflammation levels would still be elevated as a result of stress exposure after a true anti-inflammatory meal.
Aside from the limitations surrounding the test meals, additional analysis would have been helpful to best interpret the results. Foremost, no mention was made regarding a power analysis and the ability to detect differences based on the sample size. The researchers acknowledged that had a larger sample size been used, differences might have been detected between cancer survivors and controls. Theoretically, cancer survivors would exhibit different responses to inflammatory triggers as a result of their cancer history and/or cancer treatment. In addition to a larger sample size with stronger sub-group analysis, variables evaluating how stress influences the metabolic response to food would have augmented the study. For example, postprandial elevation of lipids has been associated with increased inflammatory markers leading to endothelial dysfunction.5
Despite the limitations, the study certainly advances our understanding regarding the interconnectedness of stress and nutrition. Hopefully, future studies will evaluate ways to minimize the inflammatory response to food eaten during periods of stress, as the literature generally is lacking at present. In the meantime, the practice of mindful eating is a reasonable prescription that integrative practitioners should recommend to their patients.
Integrative Medicine Alert’s executive editor David Kiefer, MD, peer reviewer Suhani Bora, MD, AHC Media executive editor Leslie Coplin, and associate managing editor Jonathan Springston report no financial relationships relevant to this field of study.