KEY LIFESTYLE STRATEGIES TO SUPPORT IMMUNE FUNCTION

Nancy Sudak, MD, IFMCPOctober 8, 2021

ATTRIBUTION

• 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

Genetic susceptibility

Chronictoxic

exposures in air, water, food, cosmetics

Chronic insufficiency of vitamins, minerals, phytonutrients

Stress & trauma

Microbes/infection

DISEASE

SOCIAL COVID-19 SUSCEPTIBILITY FACTORS

Racial or ethnic minority

Limited English proficiency

Housing occupied with high number of people

per roomHousehold without

vehicle

Lack of food access Institutionalized individuals Disabled individuals

(Karmarak)

PHYSICAL COVID-19 SUSCEPTIBILITY FACTORS

Preexisting chronic cardiac or pulmonary

diseaseHyperglycemia/diabetes

Obesity• Visceral fat higher in

patients accessing ICU

Chronic inflammation• High cytokine activity• Upregulated NLRP3

inflammasome• Bradykinin

Age/immunosenescence

Oxidative stress • 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-versahttps://www.cdc.gov/chronicdisease/resources/infographic/chronic-diseases.htm

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

Sleep

Exercise

SocialConnection

Stress Management

Food and Nutrition

Food and Nutrition

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)

(Kleinewietfeld)

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

OXIDATIVE STRESS

• 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• Smoking• Processed foods• Alcohol consumption• Pollution• Toxins• Radiation• Grilling, frying, high temp cooking

Ways to reduce oxidative stress

• Regular exercise• Stress management• Food (Halvorsen)

• Herbs/spices• Nuts/seeds• Chocolate• Vegies/fruits

• 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

(Yamamoto; Yamane)

Stress Management

STRESS• 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) • Mechanisms

• SNSEpi/NETranscription factorsSynth of inflammatory cytokines

• Activated HPA axis increases cortisolLong-term lowering of inflammatory cytokines needed to fight infection

STRESS• 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)

MEDITATIONA 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 Integrative Health

MEDITATIVE PRACTICE: MANY FORMS

• Mindfulness meditation (MBSR)• Transcendental meditation• Focused attention • Effortless presence• Loving kindness• Mantra meditation• Guided meditation• Qi Gong• Yoga• 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)

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

Resources:The Tapping Solution Appwww.eftuniverse.com, www.coursesforlife.com

Sleep

SLEEP

• 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

• 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 & Opp)

• Sleep is important for vaccine effectiveness (Zimmerman)

SLEEP• 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

Exercise

EXERCISE• 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—

Shinrin-yoku (Hansen)• 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.

SocialConnection

SOCIAL CONNECTION• 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 (Eisenberger)

• Individuals who are lonely or socially disconnected tend to show higher levels of proinflammatory cytokines

SOCIAL CONNECTION

• 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

SOCIAL CONNECTION

• 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, volunteerism

HEALTH BENEFITS OF LAUGHTER

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• 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, Bennett)

ADDITIONAL CONSIDERATIONS

• 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 isolation)!

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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), 1325–1380.https://journals.physiology.org/doi/full/10.1152/physrev.00010.2018

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. doi:1016/j.immuni.2019.09.020

REFERENCES (CONT)Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585-588. doi:1038/nature12480Dimitrov 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.2016.12.017Eisenberger 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.2016.141Freier 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.2009.10.005Gore 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.2015-1010Hansen 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/ijerph14080851Halvorsen 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/84.1.95Holmes 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

REFERENCES (CONT)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/s12160-014-9640-9Irwin 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.2020.36462Klein TW. Stress and infections. J Fla Md Assoc. 1993;80(6):409-411Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518-522. doi:1038/nature11868Leschak 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.0000000000000685Li 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

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