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Change Your Diet, Change Your Mood: Weighing the Evidence

Healthy diets are known to reduce the risk of developing a host of chronic diseases, running the gamut from metabolic syndrome to cancer, and overall mortality (Esposito & Giugliano, 2005). Adherence to an anti-inflammatory diet like the Mediterranean, for example, is associated with a significant reduction of all-cause and cause-specific mortality (Mitrou et al., 2007). If there was a drug that was associated with a significant reduction of all-cause and cause-specific mortality, it would be worth billions, if not trillions. So, let’s consider the potent and medicinal quality of food. What makes it so special? And how can it impact your mood?

The answer has to do with inflammation.

Inflammation is the shared link among the leading causes of mortality (Aggarwal et al., 2006; Giugliano et al., 2006), and likely impacts behavior. There are three key players (also called cytokines) you need to know about.

High-fat diets induce insulin resistance and obesity via production of interleukin-1β (IL-1β) in multipotent stem cells (Cortez et al., 2013), interleukin-6 (IL-6) in fat (Matsubara et al., 2012) and tumor necrosis factor-alpha (TNF-α) in muscle, liver, and fat tissue (Borst & Conover, 2005). 

IL-1β, IL-6, and TNF-α are all signaling cytokines produced by an activated immune system. All you need to know about cytokines is that they are secreted by certain immune cells and they have an effect on other body cells. They essentially keep the inflammatory processes going (Cameron & Kelvin, 2003); IL-6 and TNF-α are so powerful that they encourage breakdown of bone in vitro and in vivo (Yokota et al., 2014). Thus, it would be best to avoid letting cytokines hang around longer than they were designed to.

These immune-mediated cytokines likely influence personality traits, especially if diet-induced inflammation is habitual. Elevations in IL-6, TNF-α, and/or c-reactive protein (CRP, synthesized by the liver in response to general, non-specific  inflammation), are more commonly found in hostile-prone individuals (Suarez et al., 2002; Coccaro, 2006; Ranjit et al., 2007; Brydon et al., 2010; Janicki-Deverts et al., 2010; Mwendwa et al., 2013). This means that if you are easily upset and angered, there might be a biological basis rooted in inflammation.

In a mouse model, administration of IL-1β elicits depression-like symptoms, noted by a decrease in positively motivated behaviors like exploration, social interaction, and in operant behaviors like food reward (Larson et al., 2002; Merali et al., 2013).

A Mediterranean diet, because of its anti-inflammatory nature, reduces IL-1β, IL-6, and TNF-α (Caughey et al., 1996; Chrysohoou et al., 2004), and is a therapeutic approach to decrease “sickness behaviors” like hostility/rage and/or depression-like symptoms.

However, inconsistent results have been reported, largely because of the dearth of research on diet-induced inflammatory cytokines that affect personality presentation. Additionally, human emotion is a complicated phenomenon, and is by no means completely dictated by what we eat.

It is possible that sample characteristics of a population—age, sex, and socioeconomic status—influence the association between hostility and the inflammation we see (Graham et al., 2006; Elovainio et al., 2011; Demarble et al., 2014). For example, individuals with hostile or aggressive behavior have enhanced cardiovascular reactivity to stress (Smith et al., 2004; Chida & Hamer, 2008), and this enhanced reactivity to stressful situations can contribute to higher concentrations of proinflammatory cytokines (Black & Garbutt, 2002). 

Additionally, cytokines IL-1β, IL-6, and TNF-α are thought to activate the hypothalamic-pituitary-adrenal (HPA) axis, the central stress response system (Kunz-Ebrecht et al., 2003). With chronic activation of the stress response, people can become fatigued. Indeed, depression scores and CRP, IL-1β, and IL-6 are positively correlated (Howren et al., 2009).

Non-dietary stressors like marital discord also impacts the immune system, thereby influencing one’s emotional demeanor. Kiecolt-Glaser and colleagues (2005) found that couples who engaged in more hostile arguments had higher plasma concentrations of IL-6 and TNF-α following a conflict than couples who engaged in more non-reactive, supportive discussions. These authors suggest that more frequent and spiked increases in proinflammatory cytokines might accelerate a wide range of age-related illnesses. In other words, hostile relationships impact human physiology, setting the stage for disease later in life.

Three causal pathways are consistently shown: 

  1. Inflammation impacts emotional state
  2. Emotional state impacts inflammation
  3. Bidirectional relationship between inflammation and emotional state 

Three cytokines are thought to uniquely impact the following behavior:

  1. TNF-α → hostility
  2. IL-1β → depression
  3. IL-6 → anxiety

Anti-inflammatory diets, in combination with lessened reactivity to stress and supportive social interactions, likely reduce aggressive behaviors, depressive-like syndrome, and general anxiety.



Dr. Bhandari and the Advanced Health Team Are Here to Support Your Health

Dr. Bhandari and the Advanced Health team of experts work to help patients rid their body of inflammatory cytokines produced from the diet. They’re always ready to share their expertise on this commonly misunderstood disease. We collaborate closely together bringing the best in evidence-based Eastern and Western medicine. We believe that since each person is unique, their treatment plan should be personalized to them. To book an appointment, contact Advanced Health or call 1-415-506-9393.


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Black, P. H., & Garbutt, L. D. (2002). Stress, inflammation and cardiovascular disease. Journal of psychosomatic research, 52(1), 1-23.

Borst, S. E., & Conover, C. F. (2005). High-fat diet induces increased tissue expression of TNF-α. Life sciences, 77(17), 2156-2165.

Brydon, L., Strike, P. C., Bhattacharyya, M. R., Whitehead, D. L., McEwan, J., Zachary, I., & Steptoe, A. (2010). Hostility and physiological responses to laboratory stress in acute coronary syndrome patients. Journal of Psychosomatic Research, 68(2), 109-116.

Cameron, M. J., & Kelvin, D. J. (2003). Cytokines and chemokines—their receptors and their genes: an overview. Cytokines and chemokines in autoimmune disease, 8-32.

Caughey, G. E., Mantzioris, E., Gibson, R. A., Cleland, L. G., & James, M. J. (1996). The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. The American journal of clinical nutrition, 63(1), 116-122.

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Chrysohoou, C., Panagiotakos, D. B., Pitsavos, C., Das, U. N., & Stefanadis, C. (2004). Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study. Journal of the American College of Cardiology, 44(1), 152-158.

Coccaro, E. F. (2006). Association of C-reactive protein elevation with trait aggression and hostility in personality disordered subjects: a pilot study. Journal of psychiatric research, 40(5), 460-465.

Cortez, M., Carmo, L. S., Rogero, M. M., Borelli, P., & Fock, R. A. (2013). A high-fat diet increases IL-1, IL-6, and TNF-α production by increasing NF-κB and attenuating PPAR-γ expression in bone marrow mesenchymal stem cells. Inflammation, 36(2), 379-386.

Demarble, J. B., Moskowitz, D. S., Tardif, J. C., & D'Antono, B. (2014). The relation between hostility and concurrent levels of inflammation is sex, age, and measure dependent. Journal of psychosomatic research, 76(5), 384-393.

Elovainio, M., Merjonen, P., Pulkki-Råback, L., Kivimäki, M., Jokela, M., Mattson, N., ... & Keltikangas-Järvinen, L. (2011). Hostility, metabolic syndrome, inflammation and cardiac control in young adults: The Young Finns Study. Biological psychology, 87(2), 234-240.

Esposito, K., & Giugliano, D. (2005). Diet and inflammation: a link to metabolic and cardiovascular diseases. European Heart Journal, 27(1), 15-20.

Giugliano, D., Ceriello, A., & Esposito, K. (2006). The effects of diet on inflammation: emphasis on the metabolic syndrome. Journal of the American College of Cardiology, 48(4), 677-685.

Graham, J. E., Robles, T. F., Kiecolt-Glaser, J. K., Malarkey, W. B., Bissell, M. G., & Glaser, R. (2006). Hostility and pain are related to inflammation in older adults. Brain, behavior, and immunity, 20(4), 389-400.

Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic medicine, 71(2), 171-186.

Janicki-Deverts, D., Cohen, S., & Doyle, W. J. (2010). Cynical hostility and stimulated Th1 and Th2 cytokine production. Brain, behavior, and immunity, 24(1), 58-63.

Kiecolt-Glaser, J. K., Loving, T. J., Stowell, J. R., Malarkey, W. B., Lemeshow, S., Dickinson, S. L., & Glaser, R. (2005). Hostile marital interactions, proinflammatory cytokine production, and wound healing. Archives of general psychiatry, 62(12), 1377-1384.

Kunz-Ebrecht, S. R., Mohamed-Ali, V., Feldman, P. J., Kirschbaum, C., & Steptoe, A. (2003). Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain, behavior, and immunity, 17(5), 373-383.

Larson, S. J., Romanoff, R. L., Dunn, A. J., & Glowa, J. R. (2002). Effects of interleukin-1β on food-maintained behavior in the mouse. Brain, behavior, and immunity, 16(4), 398-410.

Matsubara, T., Mita, A., Minami, K., Hosooka, T., Kitazawa, S., Takahashi, K., ... & Nishimura, O. (2012). PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell metabolism, 15(1), 38-50.

Merali, Z., Brennan, K., Brau, P., & Anisman, H. (2003). Dissociating anorexia and anhedonia elicited by interleukin-1β: antidepressant and gender effects on responding for" free chow" and" earned" sucrose intake. Psychopharmacology, 165(4), 413-418.

Mitrou, P. N., Kipnis, V., Thiébaut, A. C., Reedy, J., Subar, A. F., Wirfält, E., ... & Schatzkin, A. (2007). Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study. Archives of Internal Medicine, 167(22), 2461-2468.

Mwendwa, D. T., Ali, M. K., Sims, R. C., Cole, A. P., Lipscomb, M. W., Levy, S. A., ... & Campbell, A. L. (2013). Dispositional depression and hostility are associated with inflammatory markers of cardiovascular disease in African Americans. Brain, behavior, and immunity, 28, 72-82.

Ranjit, N., Diez-Roux, A. V., Shea, S., Cushman, M., Seeman, T., Jackson, S. A., & Ni, H. (2007). Psychosocial factors and inflammation in the multi-ethnic study of atherosclerosis. Archives of Internal Medicine, 167(2), 174-181.

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Suarez, E. C., Lewis, J. G., & Kuhn, C. (2002). The relation of aggression, hostility, and anger to lipopolysaccharide-stimulated tumor necrosis factor (TNF)-α by blood monocytes from normal men. Brain, behavior, and immunity, 16(6), 675-684.

Yokota, K., Sato, K., Miyazaki, T., Kitaura, H., Kayama, H., Miyoshi, F., ... & Mimura, T. (2014). Combination of tumor necrosis factor α and interleukin‐6 induces mouse osteoclast‐like cells with bone resorption activity both in vitro and in vivo. Arthritis & rheumatology, 66(1), 121-129.

Dr. Payal Bhandari Dr. Payal Bhandari M.D. is a leading practitioner of integrative and functional medicine in San Francisco.

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