SUPPORT IMMUNE FUNCTION
Nancy Sudak, MD, IFMCP
October 8, 2021
• A considerable portion of this material is curated from the Institute for Functional Medicine
• Excellent resources regarding COVID-19: COVID-19 Functional Medicine Resources (ifm.org)
• Includes free presentations and patient education handouts
CONTRIBUTORS TO DISEASE
exposures in air, water, food,
insufficiency of vitamins, minerals,
phytonutrients Stress &
SOCIAL COVID-19 SUSCEPTIBILITY FACTORS
Racial or ethnic
minorityLimited English proficiency
Housing occupied with high number of people
Household without vehicle
Lack of food access Institutionalized
individuals Disabled individuals
PHYSICAL COVID-19 SUSCEPTIBILITY FACTORS
Preexisting chronic cardiac or pulmonary
• Visceral fat higher in patients accessing ICU
• High cytokine activity
• Upregulated NLRP3 inflammasome
• Glutathione deficiency
• Drives cytokine storm
PREVENTION IS THE TICKET!
• Normal isn’t healthy (CDC)
• 60% of Americans have at least one chronic condition
• 40% have two or more conditions
• 25% of children ages 2-8 have a chronic health condition
• Key underlying factors: tobacco, poor nutrition, lack of physical activity, alcohol use
• Need multi-factor upstream approach
• What supports immune function supports general health and vice-versa
FOCUS ON THE INFLAMMASOME
• Inappropriate hyperinflammatory response underlies severe cases of COVID-19
• Driven by overexuberant cytokine release
• The co-morbidities that portend greater risk are all associated with high basal inflammation
• Serum LDH indicates tissue damage supported by widespread cell death
among monocytes, alveolar epithelial cells and endothelial cells of lungs and kidneys
• Hyperexpression of TNF-a, IL-6 and IL-8 commonly seen in severe COVID (Vora)
KEY FACTORS: OVERVIEW
Management Food and
STANDARD AMERICAN DIET (SAD)
• Standard American Diet (=SAD 😢😢) is inflammatory--
sugar, high omega 6:omega 3, unhealthy fats, processed foods (Christ)
• Single highly processed meal leads to 100% rise in IL-6 within 6 hours of eating
• Pesticides can also affect immune function (Gore)
• High intake of omega 6 fats activates series 2 pro- inflammatory compounds
• High intake of fat and CHO stimulates toll-like
receptor inflammatory markers and others (Molendijk)
• Table salt induces pathogenic T helper cells (Th17)
BALANCING INFLAMMATORY PATHWAYS
• Inflammation is critical for proper immune response
• HOWEVER: prolonged or upregulated release of inflammatory mediators (IL, PG, TNF) can cause morbidity and chronic disease
• Whole foods or Mediterranean diets well studied to reduce inflammation (Bonaccio, Modndijk)
• 9-13 svgs colorful fruits and vegies
• Why so many? Powerful antiviral and immune supportive effects! (Zakaryan)
• 28-35 grams fiber from whole foods
• Fermented vegies/probiotic containing foods
• Low intake of added sugar/salt, high glycemic load
foods, excess fat
• Oxidation is the process by which we use the oxygen we breathe for energy production.
• ROS (contain only a single oxygen bond) naturally created as a function of energy production
• ROS are highly reactive, damaging
atoms/ions/molecules with one unpaired electron that targets fats, proteins and DNA (the aging process)
• Oxidative stress is an imbalance between the
natural production of free radicals (ROS) and our body’s antioxidant system
• Antioxidants from whole foods scavenges ROS and prevents cellular damage
• Oxidative stress cytokine storm perpetuate one
another in a loop of upregulated inflammation
and cellular damage
Causes of oxidative stress
• Processed foods
• Alcohol consumption
• Grilling, frying, high temp cooking
Ways to reduce oxidative stress
• Regular exercise
• Stress management
• Food (Halvorsen)
• Antioxidant supplements
• In moderation: red wine, coffee
ROLE OF THE MICROBIOME
• 70% of immune system is located in GI tract
• Dietary fibers from whole plant-based foods is fermented by bacteria for energy and SCFA production
• High fiber diets improve gut barrier fx by increasing SCFAs
• Dietary diversity is critical for a healthy gut ecology (polyphenols)
• Downregulate TNF, NF-kB, AA, TLR; inhibit oxidative stress (Yafoufi)
• Microbial diversity associated with less metabolic dysfunction (Cotillard)
• Fermented foods (yogurt, kimchi, miso, sauerkraut) can provide healthy microorganisms for these processes
• Specific strains of microorgs may affect specific viruses
• Acute and chronic stress can suppress immune function and increase susceptibility to illness (Segerstrom)
• Can alter wound healing and exacerbate AI dz, allergy, asthma (Agarwal).
• Implicated in morbidity/mortality of cancer, HIV, IBD (Marshall)
• Increased risk of viral infection (Klein, Aich)
• Brief mental stress in healthy adults can lower T-reg cell function (Freier)
• SNSEpi/NETranscription factorsSynth of inflammatory cytokines
• Activated HPA axis increases cortisolLong-term lowering of inflammatory cytokines needed to fight infection
• Allostasis ( general habituation over time)
• Common to fail to recognize stress as a primary driver impairing well-being
• Inability to regulate emotional states and labile
mood are associated with immune suppression and viral shedding (Horn, Strachan)
• The good news: stress management reduces infection and severity of infection
• Multiple studies show mind-body practices benefit immune regulation (decreased NF-kB, improved CTRA) (Buric)
• Upreg of genes that support neutrophil fx and downreg of inflammatory mediators but not immune suppression (Li)
• MBSR reduced post-stress inflammation (TNF-a
and IL-8) compared to controls (Rosenkranz)
A group of techniques, most of which started in Eastern religious or spiritual traditions. In
meditation, individuals learn to focus their
attention and suspend the stream of thoughts that normally occupy the mind. This practice is believed to result in a state of greater physical relaxation, mental calmness, and psychological balance. Practicing meditation can change
how a person relates to the flow of emotions and thoughts in the mind.
--Nat’l Center for Complementary and
MEDITATIVE PRACTICE: MANY FORMS
• Mindfulness meditation (MBSR)
• Transcendental meditation
• Focused attention
• Effortless presence
• Loving kindness
• Mantra meditation
• Guided meditation
• Qi Gong
• Progressive relaxation
• Repetitive prayer
THE RELAXATION RESPONSE
• The relaxation response is a physical state of deep rest that changes the physical
and emotional responses to stress and the opposite of the fight or flight response.
• Shifts toward parasympathetic dominance
• Timeless book: The Relaxation Response,
by Dr. Herbert Benson
EMOTIONAL FREEDOM TECHNIQUE
Tapping on acupressure points deactivates stress response
Combining with meditation enhances effectiveness
Effective for acute and chronic anxiety and PTSD
Can be very helpful for any condition:
pain of any nature, low mood, fatigue, insomnia, lack of motivation, food issues
The Tapping Solution App
• Sleep has a MAJOR influence of immune regulation and inflammatory signals.
• Enhancement of sleep during an infection is assumed to feed back to the immune
system to promote host defense (Besedovsky)
• Impaired sleep linked to short term and chronic illness (DM, CHD)
• Risk of infection is higher in individuals who sleep less than 6-7 hours/night (Prather)
• ICU patients can have prolonged
recovery from sleep deprivation (Pisani)
• Sleep is restorative and anti-inflammatory and should be considered a fundamental element of personal health (Irwin).
• Analysis of cell types and cytokines during nighttime immune activity suggest that
sleep strengthens adaptive immunity (Irwin
• Sleep is important for vaccine effectiveness
• Quality and quantity are critical—7-8 hours
• Make sleep a priority you will not compromise
• Set a regular bedtime and associated rituals
• Refrain from using devices late at night
• Sleep in cool dark room
• Limit caffeine and alcohol
• Allow 3 hours before last meal and bed
• Gentle yoga before bed
• Meditation before bed (Insight Timer is free and fantastic)
• High quality essential oil blends can be helpful
• Consider CBT-I
• Moderate regular physical activity improves immunity
• Movement promotes oxygenation, circulation of blood and nutrients, elimination of waste from cells
• One effect of pandemic for many individuals is sedentary lifestyle, which ironically can impair host defense
• Isolated exercise does stimulate rapid cellular changes to stimulate immune function, but regular
exercise has more sustained
effects (Dimitrov, Nieman)
EXERCISE—WHAT CAN YOU START NOW?
• ACSM advises 150 mins of moderate aerobic activity per week
• Less than that is better than nothing!
• 30 mins a day 5 days a week is a reasonable goal
• Do not overdo
• Outdoor exercise in clean air has additional benefits—
• Preliminary reports of yoga and tai chi/qigong supporting immune activity
• So many options—choose the most fun!
• Walking, jogging, stair climbing, chair squats, yoga
poses, yardwork, dancing, hand weight routines,
online programs, aps.
• Social isolation, loneliness, bereavement and conflict implicated in proinflammatory immune response and
increased viral susceptibility (Leschak)
• Being in a sick state increases sensitivity to social threat
• Individuals who are lonely or socially disconnected tend to show higher levels of
• Individuals who feel interconnection with people or higher meaning/purpose have
favorable gene expression, decreased stress, increased antibody responsiveness, better health (Holmes)
• Translates to lower CRP, fibrinogen, WBC activation (Walker)
• Personal variability
• Reduce exposure to hostile/toxic/non- supportive influences
• Devote time to positive/affirming people
• Routine connection such as community events, religious/spiritual/intellectual
gatherings, positive family interaction,
HEALTH BENEFITS OF LAUGHTER
• Decreases stress hormones
• Activates internal reward systems
• Anti-inflammatory effects
• Improves short term memory
• Eases depression and anxiety
• Forms social bonds
• Immune system effects—increased
secretion sIgA, NK cell activity (Ryu,
• As clinicians, walking the talk is critical
• All of these lifestyle approaches take some
commitment; having a buddy to whom to
be accountable and to share challenges
can be helpful (and an antidote to social
Agarwal SK, Marshall GD Jr. Stress effects on immunity and its application to clinical immunology. Clin Exp Allergy. 2001;31(1):25-31.
Aich P, Potter AA, Griebel PJ. Modern approaches to understanding stress and disease susceptibility: a review with special emphasis on respiratory disease. Int J Gen Med. 2009;2:19-32.
Bennett MP, Zeller JM, Rosenberg L, McCann J. The effect of mirthful laughter on stress and natural killer cell activity. Altern Ther Health Med. 2003 Mar-Apr;9(2):38-45. PMID: 12652882.
Besedovsky, L., Lange, T., & Haack, M. (2019). The Sleep-Immune Crosstalk in Health and Disease. Physiological Reviews, 99(3), 1325–
Bonaccio M, Pounis G, Cerletti C, et al. Mediterranean diet, dietary polyphenols and low grade inflammation: results from the MOLI-SANI study. Br J Clin Pharmacol. 2017;83(1):107-113. doi:1111/bcp.12924
Buric I, Farias M, Jong J, Mee C, Brazil IA. What is the molecular signature of mind-body interventions? A systematic review of gene expression changes induced by meditation and related practices. Front Immunol. 2017;8:670. doi:3389/fimmu.2017.00670
Christ A, Lauterbach M, Latz E. Western diet and the immune system: an inflammatory connection. Immunity. 2019;51(5):794-811.
Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585-588.
Dimitrov S, Hulteng E, Hong S. Inflammation and exercise: inhibition of monocytic intracellular TNF production by acute exercise via ?2- adrenergic activation. Brain Behav Immun. 2017;61:60-68. doi:1016/j.bbi.2016.12.017
Eisenberger NI, Moieni M, Inagaki TK, Muscatell KA, Irwin MR. In sickness and in health: the co-regulation of inflammation and social behavior. Neuropsychopharmacology. 2017;42(1):242-253. doi:1038/npp.2016.141
Freier E, Weber CS, Nowottne U, et al. Decrease of CD4(+)FOXP3(+) T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor. Psychoneuroendocrinology. 2010;35(5):663-673. doi:1016/j.psyneuen.2009.10.005
Gore AC, Chappell VA, Fenton SE, et al. EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals.
Endocr Rev. 2015;36(6):E1-E150. doi:1210/er.2015-1010
Hansen MM, Jones R, Tocchini K. Shinrin-yoku (forest bathing) and nature therapy: a state-of-the-art review. Int J Environ Res Public Health. 2017;14(8):E851. doi:3390/ijerph14080851
Halvorsen BL, Carlsen MH, Phillips KM, et al. Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States. Am J Clin Nutr. 2006;84(1):95-135. doi:1093/ajcn/84.1.95
Holmes L, Chinaka C, Elmi H, et al. Implication of spiritual network support system in epigenomic modulation and health trajectory. Int J Environ Res Public Health. 2019;16(21):E4123. doi:3390/ijerph16214123
Horn EE, Turkheimer E, Strachan E. Psychological distress, emotional stability, and emotion regulation moderate dynamics of herpes simplex virus type 2 recurrence. Ann Behav Med. 2015;49(2):187-198. doi:1007/s12160-014-9640-9
Irwin MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 2019 Nov;19(11):702-715. doi: 10.1038/s41577- 019-0190-z. PMID: 31289370.
Irwin MR, Opp MR. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology. 2017 Jan;42(1):129- 155. doi: 10.1038/npp.2016.148. Epub 2016 Aug 11. PMID: 27510422; PMCID: PMC5143488.
Karmaker, M. Lantz PM, Tipirneni R. Association of social and demographic factors with COVID-19 incidence and death rates in the US.
JAMA Netw Open. 2021;4(1):e2036462. Published 2021 Jan 4. doi:10.1001/famanetworkopen.2020.36462 Klein TW. Stress and infections. J Fla Md Assoc. 1993;80(6):409-411
Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature.
Leschak CJ, Eisenberger NI. Two distinct immune pathways linking social relationships with health: inflammatory and antiviral processes.
Psychosom Med. 2019;81(8):711-719. doi:1097/PSY.0000000000000685
Li QZ, Li P, Garcia GE, Johnson RJ, Feng L. Genomic profiling of neutrophil transcripts in Asian qigong practitioners: a pilot study in gene regulation by mind-body interaction. J Altern Complement Med. 2005;11(1):29-39. doi:1089/acm.2005.11.29
Marshall GD Jr. The adverse effects of psychological stress on immunoregulatory balance: applications to human inflammatory diseases.
Immunol Allergy Clin North Am. 2011;31(1):133-140.
Molendijk I, van der Marel S, Maljaars PWJ. Towards a food pharmacy: immunologic modulation through diet. Nutrients.
Nieman DC, Wentz LM. The compelling link between physical activity and the body’s defense system. J Sport Health Sci. 2019;8(3):201- 217. doi:1016/j.jshs.2018.09.009
Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF. Sleep in the intensive care unit. Am J Respir Crit Care Med. 2015 Apr 1;191(7):731-8. doi: 10.1164/rccm.201411-2099CI. PMID: 25594808; PMCID: PMC5447310
Prather AA, Janicki-Deverts D, Hall MH, Cohen S. Behaviorally Assessed Sleep and Susceptibility to the Common Cold. Sleep. 2015 Sep 1;38(9):1353-9. doi: 10.5665/sleep.4968. PMID: 26118561; PMCID: PMC4531403.
Rosenkranz MA, Davidson RJ, Maccoon DG, Sheridan JF, Kalin NH, Lutz A. A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation. Brain Behav Immun. 2013 Jan;27(1):174-84. doi: 10.1016/j.bbi.2012.10.013.
Epub 2012 Oct 22. PMID: 23092711; PMCID: PMC3518553.
Ryu KH, Shin HS, Yang EY. Effects of Laughter Therapy on Immune Responses in Postpartum Women. J Altern Complement Med. 2015 Dec;21(12):781-8. doi: 10.1089/acm.2015.0053. Epub 2015 Oct 23. PMID: 26496141.
Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull.
Strachan E, Saracino M, Selke S, Magaret A, Buchwald D, Wald A. The effects of daily distress and personality on genital HSV shedding and lesions in a randomized, double-blind, placebo-controlled, crossover trial of acyclovir in HSV-2 seropositive women. Brain Behav Immun.
Vora, S.M., Lieberman, J. & Wu, H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol (2021).
Walker E, Ploubidis G, Fancourt D. Social engagement and loneliness are differentially associated with neuro-immune markers in older age: time-varying associations from the English Longitudinal Study of Ageing. Brain Behav Immun. 2019;82:224-229.
Yahfoufi N, Alsadi N, Jambi M, Matar C. The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients.
Yamamoto Y, Saruta J, Takahashi T, et al. Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial. Acta Odontol Scand.
Yamane T, Sakamoto T, Nakagaki T, Nakano Y. Lactic acid bacteria from kefir increase cytotoxicity of natural killer cells to tumor cells.
Foods. 2018;7(4):E48. doi:3390/foods7040048
Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017 Sep;162(9):2539- 2551. doi: 10.1007/s00705-017-3417-y. Epub 2017 May 25. PMID: 28547385; PMCID: PMC7087220.
Zimmermann P, Curtis N. Factors That Influence the Immune Response to Vaccination. Clin Microbiol Rev. 2019 Mar 13;32(2):e00084-18.
doi: 10.1128/CMR.00084-18. PMID: 30867162; PMCID: PMC6431125.