Psychoneuroimmunology (PNI) & Inflammation

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Psychoneuroimmunology (say that three times fast, or just call it PNI) is the scientific study of your mind, body and overall health. Specifically it is the study of “the interaction between psychological processes and the nervous and immune systems of the human body.”

As a biohacker, if I wasn’t already happily unavailable, I’d want to date a psychoneuroimmunologist. That has to be the sexiest profession ever. One of the core tenets of the Bulletproof program is that if you get your “hardware” working right (your body), then your brain is capable of more than you’ve ever dreamed possible.

PNI is the research helping you upgrade your mind and body through food and stress control – the Bulletproof way. This supports the Bulletproof Diet because it is more than eating the right foods – it is a lifestyle that involves becoming more resilient and happier by increasing awareness of how your mind and body are affected by food and your environment. That’s the Bulletproof state of high performance I keep talking about.

According to PNI, upgrading your body begins with avoiding proinflammatory foods – the dominant principle in the Bulletproof Diet. A recent study done shows that insulin is a key pathway leading to stress and negative influences in the body.(1) Your diet modulates key pathways to inflammation through sympathetic activity, oxidative stress, and proinflammatory cytokine production.(5) Stress and depression are also correlated to higher insulin levels.(23)

Problems with Inflammation

High insulin levels in the body are at the center of many diseases. Together, cardiovascular disease, cancer, and diabetes account for almost 70% of all deaths in the United States – inflammation is a common link between these diseases.(15,17)  Inflammation is also linked to many autoimmune diseases and some mental health issues.(30)

Diets that promote inflammation are high in refined starches, sugar, and trans-fats. Refined starches and sugars can alter blood glucose and insulin levels, and postprandial hyperglycemia can increase production of free radicals as well as proinflammatory cytokines.(15, 25)

In order to avoid inflammation, and therefore many diseases, eating a diet with high ratios of omega-3 to omega 6 fatty acids and natural antioxidants is important.

Omega-3 fatty acids found in fish oil, avocado, and grass-fed beef curb the production of AA-derived eicosanoids, which spike insulin.(27) American’s levels of omega-3 to omega-6 fatty acids are abysmal and contribute to many diseases of inflammation. These fatty acids compete for the same pathways, and thus their balance is important.(28)

Think I’m kidding? On the Bulletproof Diet, my WellnessFX test showed my ratio of omega 6 to omega 3 was 1.28. Anti-aging doctors hope for 4:1, and the average American can be as high as 40:1.

A study done in China found that lower n-6 to n-3 ratios (ie eating less omega 6) are associated with lower proinflammatory cytokine production and demonstrate significant inverse relationships between annual fish consumption and depression.(9) The more fish eaten, the lower the prevalence of serious clinical depression. Stress and depression were associated with less fruit and more snack consumption.

You may want to try low-mercury fish like anchovies, tilapia, and trout to avoid harmful metals, or go with my favorite, krill oil.

Stress and Your Gut

The vagus nerve is involved in digestion, absorption, and metabolism of nutrients.(7) Unhealthy food, stress, and depression have negative effects on vagal activation. This shows that there is a direct correlation between your brain and gut because stress hinders your guts essential actions.

Stress also influences your food choices, and increases  insulin resistance. Stress increases maladaptive metabolic responses to unhealthy meals, which affects mood and proinflammatory responses to stressors.(1) Avoid or hack your stress at home and in the workplace in order to get the most from the nutrients in food.

Two ways I have successfully reduced stress are through learning to control my breathing and heart rate. For breathing, focus on using your whole diaphragm and slowly letting air in and out through your nose. It may help to place your hand on your belly and make sure your belly rises and falls while breathing in and out. Good practices for this are yoga (pranayama) and taking a class called “The Art of Living.” (If you have more share them!)

Learn to control your heart rate with the help of technology. A device called the emWave2 measures the space between heartbeats, and through feedback, can help you increase your heart-rate variability. Increased HRV is associated with being able to respond to situations in a healthy way []. There is a correlation between mental health and good heart rate variability.

As a biohacker, I am an advisor to the company that invented Heart Rate Variability training, and I insist that my executive performance coaching clients use the emWave2 because of the systemic effects it has on so many levels.

Combine the Bulletproof Diet with two of my biohacks – learning to breathe properly and improving your heart-rate variability – and your brain and gut will work better together. You will interpret this as feeling Bulletproof.

Psychoneuroimmunology is a relatively new field, and gives us an idea on how stress and food affect the body. Minimizing inflammatory foods and enhancing vital nutrients like omega-3 fatty acids and antioxidants, not only helps you avoid disease – you live more optimally. Add a life you enjoy into the equation and you can push your body and mind to new heights :). Hack on biohackers.

If you have questions about psychoneuroimmunology or have some cool insights about foods effect on your brain function share them below!


Click to read the complete list of references.

  1. Kiecolt-Glaser JK. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosom Med. 2010 May;72(4):365-9. Epub 2010 Apr 21. Review. PubMed PMID: 20410248; PubMed Central PMCID: PMC2868080.
  2. Fritsche K. Fatty acids as modulators of the immune response. Annu Rev Nutr. 2006;26:45-73. Review. PubMed PMID: 16848700.
  3. Mikolajczyk RT, El Ansari W, Maxwell AE. Food consumption frequency and perceived stress and depressive symptoms among students in three European countries. Nutr J. 2009 Jul 15;8:31. PubMed PMID: 19604384; PubMed Central PMCID: PMC2716364.
  4. Mozaffarian D, Aro A, Willett WC. Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr. 2009 May;63 Suppl 2:S5-21. Review. PubMed PMID: 19424218.
  5. Calder PC, Albers R, Antoine JM, Blum S, Bourdet-Sicard R, Ferns GA, Folkerts G, Friedmann PS, Frost GS, Guarner F, Løvik M, Macfarlane S, Meyer PD, M’Rabet L, Serafini M, van Eden W, van Loo J, Vas Dias W, Vidry S, Winklhofer-Roob BM, Zhao J.Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009 May;101 Suppl 1:S1-45. Review. PubMed PMID: 19586558.
  6. Fontana L. Neuroendocrine factors in the regulation of inflammation: excessive adiposity and calorie restriction. Exp Gerontol. 2009 Jan-Feb;44(1-2):41-5. Epub 2008 Apr 12. Review. PubMed PMID: 18502597; PubMed Central PMCID: PMC2652518.
  7. Teff KL. Visceral nerves: vagal and sympathetic innervation. JPEN J Parenter Enteral Nutr. 2008 Sep-Oct;32(5):569-71. Review. PubMed PMID: 18753395.
  8. O’Keefe JH, Gheewala NM, O’Keefe JO. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol. 2008 Jan 22;51(3):249-55. Review. PubMed PMID: 18206731.
  9. Liu C, Xie B, Chou CP, Koprowski C, Zhou D, Palmer P, Sun P, Guo Q, Duan L, Sun X, Anderson Johnson C. Perceived stress, depression and food consumption frequency in the college students of China Seven Cities. Physiol Behav. 2007 Nov 23;92(4):748-54. Epub 2007 Jun 2. PubMed PMID: 17585967.
  10. Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007 Nov;86(5):1286-92. PubMed PMID: 17991637.
  11. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun. 2007 Oct;21(7):901-12. Epub 2007 May 1. Review. PubMed PMID: 17475444.
  12. Kiecolt-Glaser JK, Belury MA, Porter K, Beversdorf DQ, Lemeshow S, Glaser R. Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults. Psychosom Med. 2007 Apr;69(3):217-24. Epub 2007 Mar 30. PubMed PMID: 17401057; PubMed Central PMCID: PMC2856352.
  13. Michaeli B, Berger MM, Revelly JP, Tappy L, Chioléro R. Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. Clin Nutr. 2007 Feb;26(1):70-7. Epub 2006 Oct 18. PubMed PMID: 17055120.
  14. Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL.Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67. Review. Erratum in: J Clin Psychiatry. 2007 Feb;68(2):338. PubMed PMID: 17194275.
  15. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006 Nov 30;72(11):1605-21. Epub 2006 Aug 4. Review. PubMed PMID: 16889756.
  16. Pace TW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH, Heim CM. Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry. 2006 Sep;163(9):1630-3. PubMed PMID: 16946190.
  17. Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006 Aug 15;48(4):677-85. Epub 2006 Jul 24. Review. PubMed PMID: 16904534.
  18. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan;27(1):24-31. Epub 2005 Nov 28. Review. PubMed PMID: 16316783; PubMed Central PMCID: PMC3392963.
  19. Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005 Mar;135(3):562-6. PubMed PMID: 15735094.
  20. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004 Oct;80(4):1029-35. PubMed PMID: 15447916.
  21. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9090-5. Epub 2003 Jul 2. PubMed PMID: 12840146; PubMed Central PMCID: PMC166443.
  22. Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003 Jul 15;108(2):155-60. Epub 2003 Jun 23. PubMed PMID: 12821543.
  23. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, Petrov D, Ferstl R, von Eynatten M, Wendt T, Rudofsky G, Joswig M, Morcos M, Schwaninger M, McEwen B, Kirschbaum C, Nawroth PP. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1920-5. Epub 2003 Feb 10. PubMed PMID: 12578963; PubMed Central PMCID: PMC149934.
  24. Esposito K, Nappo F, Giugliano F, Giugliano G, Marfella R, Giugliano D. Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects. Am J Clin Nutr. 2003 Jan;77(1):139-43. PubMed PMID: 12499333.
  25. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72. PubMed PMID: 12379575.
  26. Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology. Annu Rev Psychol. 2002;53:83-107. Review. PubMed PMID: 11752480.
  27. Maes M, Christophe A, Bosmans E, Lin A, Neels H. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress. Biol Psychiatry. 2000 May 15;47(10):910-20. PubMed PMID: 10807964.
  28. Mori TA, Puddey IB, Burke V, Croft KD, Dunstan DW, Rivera JH, Beilin LJ. Effect of omega 3 fatty acids on oxidative stress in humans: GC-MS measurement of urinary F2-isoprostane excretion. Redox Rep. 2000;5(1):45-6. PubMed PMID: 10905544.
  29. Hibbeln JR. Fish consumption and major depression. Lancet. 1998 Apr 18;351(9110):1213. PubMed PMID: 9643729.
  30. Zhang J. Yin and yang interplay of IFN-gamma in inflammation and autoimmune disease. J Clin Invest. 2007 Apr;117(4):871-3. PubMed PMID: 17404615; PubMed Central PMCID: PMC1838954.
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By Dave Asprey

  • Ian Butterworth

    Yes meditation is important. I have been doing Sahaja Yoga meditation for many years and it has been great for stress reduction. See:

  • AdamFiddler

    Awesome article. This is such a fascinating subject. I appreciate the detailed list of citations at the end of the article. Are there any reasonably comprehensive books that you would recommend on the subject?


  • Ulrik

    I love my emwave2, but I don’t always have it with me, and it’s rather expensive. I’ve found that the iPhone app, Stress Doctor from azumio, works very well in picking up my heart rate rhythm via the iPhone camera, so that’s a cheap and convenient way to practice coherence. Note, I’m not affiliated with azumio in any way; I just think it’s a cool app, and a cheap way to do HRV training (if you already have an iPhone, that is).

  • nthmostfit

    Right ON. This jibes so well with the experimental diet/fitness framework I am developing and beta-testing on myself and my clients.

  • Kathie

    As usual, great info. Keep it coming.
    Question…have been going through all the archives and wanting to do your “Level One Asprey Cocktail”…do you try to do all 6 things at once over the day? you have a protocol for time of day and with or without food? I have known mycotoxin infection BTW.Just getting started with Dr.Shoemakers work. Thanks for all your wonderful info. I now have hope.

  • Degleby Nerbinstein

    your krill oil link is broke

  • Hey Dave,

    What is your take on the interaction between “loving kindness” meditation and Vagal tone/HRV? Dr Barbara Fredrickson has done research linking LKM to improved HRV even without the practitioner having any direct biofeedback.

    You should really get her on your podcast!

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  • Joejoe

    Get to much of a product marketing impression from the site when I met Dave he passionately genuinely believes in this stuff recommend letting the passion speak for the products. Not the other way

  • Randy

    This entire bulletproof program has been life-changing for me. Before starting the program I was already way ahead of most when it came to overall nutrition and fitness, but I still suffered from mild depression, stress & anxiety, and brain fog. I was also frequently tired throughout the day. I started off with baby steps, just by adding coconut oil to my morning coffee. The effects of that one tbsp of coconut oil had a very dramatic effect on my focus and energy levels throughout the day. I then increased my intake of grass-fed butter, grass-fed beef, free-range eggs, and fresh vegetables. I have also completely cut wheat out of my diet after listening to the “Wheat Belly” podcast. I’ve been trying my best to be bulletproof for the last month and a half and throughout that time, I could feel myself steadily becoming more focused and energized and my current overall well-being is through the roof right now. I really can’t remember the last time I’ve felt this happy. I also have a very stressful job with odd hours and I use the emwave2 religiously at least twice a day, with great results. I find that if I do a 10 min emwave session just before work, my day tends to go by a lot more smoothly and I’m much more resilient to stressful situations. I just bought the book, “Wheat Belly” for my mom who’s a diabetic (almost my entire family is diabetic) and I’m hoping that my loved ones can adopt some of the bulletproof ways of living.

  • Steve


  • Steve

    I am at a mild risk for prostate cancer and my question is will the bulletproof diet optimize hormones including testosterone which is part of the process of prostate cancer growing. On another note is there any where on the site that details making your own chocolate with appropriate amounts, ratios and technique. Thank you

  • Dave Crouch

    First comprehensive read of this site, and love it. Thank you for taking the time and energy to build and maintain it. I’ve been “bio-hacking” for most of my life, without having a name for it. I started with an assumption, at about 12 years of age, that we weren’t evolving, but rather devolving — that the absence of natural foods, motions, and connection to internal thinking and mind-body processes was causing us to drift away from a greater genetic potential than we had cause to awaken. Meditation, Yoga, NLP & Hypnosis, Super-Learning, Flow States, Hemi-Sync Discovery & Gateway programs, Esoteric martial art practices, super-nutrition, counting heartbeats with an old Daoist technique… lots of familiar assertions.

    Reviewing the posts on coherence and heartbeats, making the “involuntary”, voluntary, I’ve used a stethoscope most of my life. Inhale over a 9 heartbeat span, hold for 9 heartbeat, exhale over 9 beats, hold for 9. Most people have to start at 4 or 6, and learn to relax into the spans which rely on reserve volume. But the technique works well, increases mindfulness within, and one can usually find a decent used steth cheap on Amazon, or at a local used stuff store.

    Looking forward to learning more, and diving back into hacking… esp since there’s a name for it, now.

    • Lady T

      Hi Dave, Great post. Thank you for sharing your breathing practice I will give it a try : )

  • fatima

    Just live totally in the NOW moment.
    When you speak, each word must be heavy with felt meaning,
    when you listen, each sound must be listened with full attention.
    everything is only a happening…
    let us not give labels such as tragedy, saddness, sorrow…
    Result-Bulletproof existence and performance is at your door…

  • Unicorn

    I have been doing the gentle breath meditation for years now, bought through by Serge Benhayon and Universal Medicine, which along with dietary changes has made a hugs impact on my life and thus with everyone with whom I am in contact