Immune System Health

A Whole Health approach to immune system health encourages clean living, healthy eating, adequate sleep, exercise, positive relationships, and stress reduction.

Whole Health emphasizes mindful awareness and Veteran self-care along with conventional and integrative approaches to health and well-being. The Circle of Health highlights eight areas of self-care: Surroundings; Personal Development; Food & Drink; Recharge; Family Friends, & Co-Workers; Spirit & Soul; Power of the Mind; and Moving the Body. The narrative below shows what a Whole Health clinical visit could look like and how to apply the latest research on complementary and integrative health (CIH) to immune system health.

Meet the Veteran

man portrait

Greg is a 45-year-old Gulf War Veteran who is new to your practice.  He is feeling frustrated with his propensity toward frequent upper respiratory tract infections (URI) and difficulty controlling his asthma.  For the last couple of months, he has found himself using his albuterol inhaler 3-4 times per week, maybe a bit more when he was having URI symptoms—which was about three discrete episodes over that time frame.  He has had periods similar to that nearly every year for the last 10 years.  He denies ever being hospitalized for his asthma, although there were several times over the last 20 years when he required prednisone for an acute exacerbation.  He has tried some over-the-counter antihistamines, which seem to help a bit, but he does not like the way they make him feel.  He has been on an inhaled steroid in the past but stopped a couple years ago because he was feeling better.

Greg notes he feels overall fatigued and he is tired of “always having a cold” and “getting whatever everyone else has, only worse.”  He wonders if something is wrong with his immune system that is causing this.  He would like to have the energy to play with his children and not be afraid that exercise will worsen his breathing.  Clinicians have put him on inhaled steroids when he has had previous episodes, which provided some relief, but he feels this was a really passive approach and may not be getting at an underlying health issue.

Personal Health Inventory

On his Personal Health Inventory (PHI), Greg rates himself a 2 out of 5 for his overall physical well-being and a 3 for overall mental and emotional well-being. When asked what matters most to him and why he wants to be healthy, Greg responds:

“Feeling like a strong, healthy person that my kids can see as an example of good health and strength. My family, my wife, and children are important to me. My relationships with my brother and my dad, too, but those have been trickier lately.”

For the eight areas of self-care, Greg rates himself on where he is, and where he would like to be. He decides to first focus on the areas of Working the Body and Power of the Mind by training for a bike race. He also plans to work with his doctor to better understand his asthma and find ways reduce his symptoms.

For more information, refer to Greg’s PHI.

Introduction

The human immune system is an elegant and complicated defense that not only protects us from foreign invaders such as bacteria, viruses, and parasites, but also is largely responsible for repair of the daily wear and tear from typical use of the body and healing of injuries.  The immune system also continually patrols the body to find, and essentially destroy, cells that show signs of having lost regulatory mechanisms that, eventually, may be the seeds of cancer.

The anatomy of the immune system includes a variety of components including, but not limited to, the following:

Specific cells types that circulate in the blood and patrol local tissues: Generally termed leukocytes (aka, white blood cells), these cells types can be generally broken down into components of innate and adaptive immune responses.

  • The innate immune response is nonspecific and includes cells that can quickly recognize threats such as cancerous cells and invading infections. They recognize general patterns that pose threats and respond generically by isolating and/or destroying their target.  Cell types involved in this response include neutrophils, eosinophils, mast cells, natural killer cells and macrophages. Through activation and inflammation, they produce effector molecules such as prostaglandins and leukotrienes—some of which are inflammatory and some of which control inflammation.
  • The adaptive immune response is more specific, generally triggered by the innate immune response (if it becomes overwhelmed) and takes longer to be activated (in the realm of days). It also holds “memory” so that if encountering the same threat in the future, it activates much more quickly.  This aspect of the immune system is what we refer to when we are “immune” to a disease through vaccination or previous exposure to an illness (e.g., chicken pox). The main cell types are B cells and T cell (aka lymphocytes).
  • The innate and adaptive systems work together and communicate through soluble molecules called cytokines.  They also give feedback on each other to regulate the responses to avoid over-reaction or persistence of inflammation.[1]

Physical Barriers:  Separations between the external work and our internal environments.  This includes our skin and the linings of our respiratory and gastrointestinal (GI) tracts. These barriers are more than a simple layer of cells—they include secreted coatings, molecules, and a complex balance of bacteria called a microbiome that influence local and systemic immune function.

Solid organs and areas of concentrated immune activity:

  • Lymph nodes: These small nodules, found all over the body, serve as a place for T and B cells to meet antigens. Also within these nodes, lymphocytes increase in number as needed in response to infections, and usually are clustered in groups at sites where numerous blood and lymph vessels converge such as in the neck axilla and groin among other areas.
  • Thymus: This organ found within the chest cavity grows until puberty, then progressively involutes until adulthood when it is largely fatty tissue and a small amount of remaining immune tissue. The main role of the thymus is to select out T cells that are able to recognize self vs, nonself—i.e., assure we have an army of T cells that can recognize invaders and avoid attacking us.
  • Spleen: About the size of a fist, the spleen is located in the left upper quadrant of the abdomen. It functions similarly to lymph nodes as a meeting place for antigens, T cells and B cells and a place for lymphocyte proliferation, but it does not connect to the lymph system.  While it contains about 25% of total lymphocytes, it also contains high numbers of macrophages.  This combination of functions makes the spleen a sort of infection filter for the blood.
  • Mucosa-associated lymphoid tissue (MALT): These specialized components of the immune system that line the respiratory, gastrointestinal (GALT), and reproductive tracts.[1]

When the system is underactive, we are obviously more vulnerable to immune system diseases.  However, “too much of a good thing” can have adverse consequences as well.

Acute inflammation, as in the case of the swelling that comes after a twisted ankle or the activation of the immune system in an episode of strep throat, is part of the healing process.  A low level of chronic inflammation, however, without useful purpose to the individual, is something different.  The literature defines this type of as two- to fourfold elevation in circulating levels of proinflammatory and anti-inflammatory cytokines, natural occurring cytokine antagonists, and acute-phase proteins, as well as minor increases in counts of neutrophils and natural killer cells.  The level of these increases are far from those seen in acute infections or injuries but are strongly associated with various lifestyle and demographic factors and with increased risk of heart disease, diabetes, and chronic obstructive pulmonary disease (COPD), and all-cause mortality.[2]  Immune function, therefore, is crucial to maintain and optimize.  Here we will take a deeper look into ways in which various aspects of our lives can support or inhibit optimal immune function.

Chronic inflammation makes a significant contribution to the progress of many common chronic diseases, including cardiovascular disease, stroke, diabetes, depression, cancer, and various types of arthritis.

Self-Care

Moving the Body

The impact of exercise on immune function has several areas to consider.  We will start with the example of the risk of acquiring an acute illness such as an upper respiratory infection (URI) or the common cold.  Growing evidence indicates that moderate amounts of regular exercise improve immune function and decrease the risk of developing a URI.[3]  There is a transient depression of immune function with associated increased risk of URI after periods of intense, prolonged exercise such as training for and/or running in a marathon.[4]  It appears that exercise lasting more than an hour mildly suppresses lymphocyte proliferation.[5]  However, more-recent evidence suggests improved immunity in intensely training athletes, even in those training with the added hypoxic stress of being at altitude.[6] Of note, even the possible transient decline may be avoidable with adequate carbohydrate intake[7] somewhere in the range of 30-60 gm of carbohydrate per hour during such exercise.[8]

Next, we can consider that regular aerobic exercise decreases the risk of chronic illnesses such as insulin resistance, cardiovascular disease, neurologic decline, and tumor growth.  The mechanism by which it does this is in part by decreasing the amount of the more dangerous visceral fat that is stored around the internal organs, which is in and of itself highly inflammatory.[3]  However, there is some evidence that exercise also has direct anti-inflammatory effects.  The mechanism, yet to be elucidated, may involve the following:

  • Reduced accumulation of inflammatory cells in fat tissue
  • Release of immune molecules that attenuate inflammation
  • Stimulation of the parasympathetic (“rest and digest”) portion of the nervous system
  • Improvement in ability of the individual’s body to adapt (i.e., exercise acts as a stressor to which the body can respond and improve its function)[9]

Exercise may have a role in cancer care as well.  While further research is needed, there is some evidence that immune function in patients being treated for or with a history of cancer can affect rates of recurrence.  Several studies of patients either going through chemotherapy or with a history of cancer show regular physical activity is associated with improvement in several cancer-specific immune components[10]. Exercise has shown to decrease the suppression of markers of innate immune cell function by intratumoral lactate levels.[11]   Reduction in proinflammatory markers may be most significant when a combination of aerobic and resistance training is employed.[12]  Overall, exercise has the potential to target tumor growth by supporting the function of cytotoxic immune cells and controlling acute and chronic inflammation. [13]

While the above studies focused on aerobic, moderate-intensity exercise, other forms of movement benefit immune function.  There is evidence that qi gong, tai chi, and yoga practices, which involve intentional meditative movement and breathing, improve immune function through a variety of immune pathways.[14][15][16]  A recent review of 15 randomized control trials (RCTs) that looked at the impact of yoga on various markers of immune function found that regular yoga practice can downregulate proinflammatory markers such as IL-6 and TNF-alpha.[17]  This may be particularly important for those with physical conditions that preclude more-intense exercise regimens.

Moving the body can have a significant influence on immune function for many different illnesses, and beneficial approaches include tai chi, qi gong, and yoga, as well as aerobic, moderate-intensity exercise.

Surroundings

Environmental exposures can clearly influence immune function.  Certainly, those with environmental allergies such as dust mites or pet dander do much better with avoidance of those allergens.  For those individuals, allergy testing with an allergy specialist may make sense.  However, there are a number of common chemicals, which are nearly omnipresent, that have been found to negatively impact immune function as well—potentially even leading to imbalances of the immune system, predisposing us to higher levels of autoimmune diseases such as allergies and asthma.[18]  Perfluorinated compounds (PFCs) are chemicals found in nonstick pans, furniture, cosmetics, household cleaners, clothing, and packaged food containers.  Dioxins are by-products of paper manufacturing and in the combustion of many different forms of waste that are extremely persistent and widely found in the environment due to atmospheric dispersion, deposition, and subsequent accumulation in the food chain.  They have been found in soil, sediment, fish, meat, cow’s milk, human fat tissue and breast milk.  Both of these chemical classes have been found, in addition to other adverse health effects, to suppress immune function,[19] as has long-term exposure to particulate matter in the air.[20]  These are only a few examples of chemical pollutants—there are tens of thousands more which have unproven safety profiles.

Becoming more aware of the number of chemicals to which we are exposed and their potential for negative impact on our health can be overwhelming.  When working with individuals on this aspect of environmental health, it is prudent to focus on what can be controlled—i.e., limiting exposures using resources such as the website of the Environmental Working Group and supporting overall health so that the body’s inherent detoxification mechanisms can operate optimally.

Personal Development

Stress in general has been found to have an impact on many aspects of physical and emotional health, even to the point of decreasing the antibody response to immunization with influenza vaccines.[21]  Job stress (such as high demands, low control, high strain, job dissatisfaction, effort-reward imbalance, over-commitment, burnout, unemployment, downsizing, recessions, etc.) has been found to reduce a variety of immune functions while increasing inflammatory markers.[22]  The studies looking at this were challenged by the sheer number of economic, psychosocial, and comorbid medical issues that influence job (or lack of employment) related stress.  However, because employment is both a source of income that is required to support our basic needs and many times a large part of how we see ourselves and/or contribute to society, it is important to understand how work affects the health of individuals.

As mentioned above, inflammation is a large part of the pathophysiology of many chronic diseases, including asthma.  Asthma symptoms are more likely to flare in the face of psychosocial stress such as low socioeconomic status and urban living.  Immune changes with stress-induced flares may actually make the individual less responsive to the corticosteroids used to treat that exacerbation.[23] Therefore, despite appropriate medication regimens, it may not be possible to control asthma adequately without addressing emotional stressors.  It would not be a stretch to see this applying to other chronic diseases as well.

Food & Drink

Let food by thy medicine and medicine be thy food.

—Hippocrates

Nutrition may be the single, most-important factor in optimizing immune function and controlling inflammation in the body because it can have a positive or negative impact depending on dietary patterns.  The food we eat can be broken down roughly into micronutrients (vitamins and minerals, which are only required in small amounts) and macronutrients (protein, carbohydrate, and fats).

A large number of micronutrients have been studied in terms of their impact on immune function.  The following is a summary of some of the more recent data on several important immune-mediating micronutrients.

Vitamin A

Vitamin A deficiency has been linked to decreased function of both innate and adaptive immune cells, leading to increased susceptibility to infections.  Supplementation in deficient children has been shown to decrease morbidity and mortality from infectious diseases.[24]

Note that supplements containing vitamin A might put individuals at risk for toxicity.  Therefore, supplements should contain beta-carotene or other provitamin A carotenoids that the body can then convert to the active vitamin as needed.  The recommended daily allowances (RDA) for vitamin A are given as retinol activity equivalents (RAE).  For adult men, this is 900 mcg RAE, and for women, 700 mcg RAE. Dietary sources of vitamin A include liver, sweet potatoes, spinach, pumpkin, and carrots.[25]

Vitamin B6

Deficiency of vitamin B6 can lead to low white blood cell counts, decreased innate immune function, and lowered antibody response to antigens.ref id=[24]  Note that excess vitamin B6 supplementation can result in severe and progressive sensory neuropathy characterized by loss of control of bodily movements.  The RDA of vitamin B6 is 100 mg per day for adults.  Dietary sources of vitamin B6 include chickpeas, liver, tuna, salmon, chicken breast, fortified cereals, and potatoes.[26]

Vitamin B12 and Folate (formerly known as Vitamin B9)

Vitamin B12 deficiency, in addition to leading to macrocytic anemia and paresthesias, can contribute to depressed immune responses such as decreased T cell proliferation. Deficiencies in folate manifest similarly to those of B12—macrocytic anemia and depressed immune response.[24]

Vitamin C

Vitamin C plays an important role in many aspects of the innate and adaptive immune systems and acts as a potent antioxidant.  Vitamin C deficiency results in higher susceptibility to infections.  Vitamin C deficiency can also lead to increased oxidative damage and severity of infection (especially of the lower respiratory tract), decreased resistance to infection and cancer, and impaired wound healing.  Supplementation may protect immune cells from oxidative stress, reduce incidence and duration of pneumonia in older people, and reduce duration and severity of respiratory infections, diarrhea, and malaria in children.  Vitamin C demand rises during acute infections due to increased metabolic requirement.  Doses required to saturate plasma levels and optimize cell and tissue levels in order to prevent infection are somewhere in the realm of 100-200 mg/day. [24]

Vitamin C is one of the few specific therapies used to treat patients with COVID 19, the illness caused by the novel coronavirus, which seems to have originated in Wuhan, China in late 2019 and caused a worldwide pandemic.  Intravenous vitamin C seems to have a potent anti-inflammatory effect in the lungs and may help mitigate some of the significant pulmonary damage caused by this virus in critically ill individuals, although this requires more data to determine timing and required dosing. [27]

Foods rich in vitamin C include citrus fruits, tomatoes, potatoes, red and green peppers, kiwifruit, broccoli, strawberries, Brussels sprouts, and cantaloupe.[28]

Vitamin D

Vitamin D deficiency has been associated with increased susceptibility to infections (especially of the respiratory tract), increased severity of infections, reduced mass of immune system organs and cells, and increased risk of autoimmune diseases. It also has been implicated in increased susceptibility to and poorer immune function in HIV infection.  Through activation of the nuclear vitamin D receptor (VDR) and the vitamin D metabolizing enzymes (both of which are present in nearly all immune system cells), vitamin D has significant immunomodulatory effects in essentially all aspects of the immune system.  When deficient, supplementation has been shown to decrease respiratory tract infections.  However, supplementation in vitamin D sufficient individuals is of unclear value and the data for benefit on disease risk and severity is hopeful but far from complete.[24][29][30]

Higher levels of 25-hydroxy-vitamin D have been associated with improved survival in colorectal cancer (CRC) patients, both pre- and post-diagnosis.  Vitamin D is a modulator of both the innate and adaptive immune response and exerts a range of anticancer effects including anti-proliferation, induction of differentiation, induction of apoptosis, suppression of angiogenesis and anti-inflammation.[11]

The RDA for vitamin D is between 600 and 800 IUs daily for adults (15-20 mcg).  However, given that a major source of vitamin D is exposure to sunlight, deficiency is not uncommon in latitudes farther from the equator.  Serum levels of 25-hydroxyvitamin D [25(OH)D] of less than 20 ng/mL are considered deficient but many labs indicate <30 as being “low.”   It is reasonable to alter supplementation dose in order to maintain a level above 30.  While risks of vitamin D toxicity are relatively low, levels >60 ng/mL may have some adverse effects.[31]

Vitamin E

While vitamin E deficiency is rare, when present, it negatively affects function of both innate and adaptive immune responses.  Supplementation has been linked to decreased respiratory tract infections in older people.[24]  The RDA for vitamin E is 15 mg daily.  Vitamin E is best obtained through food; rich dietary sources include nut oils, sunflower seeds, almonds, hazelnuts, and peanuts.[32]  If dietary supplements are used, look for products that contain mixed tocopherols.

Copper

Deficiency in copper can lower numbers of neutrophils, which are key players in the innate immune response.  Supplementation can be beneficial to immune function in those who are deficient but over supplementation has been shown in some subsets of humans to decrease the antibody response to the influenza vaccine.[24]  The RDA for copper is about 900 mcg and dietary sources include shellfish, seeds and nuts, organ meats, wheat-bran cereals, whole-grain products, and chocolate.[33]

Iron

Iron deficiency can lower the capacity of the immune system to mount an adequate response to infection.  However, over-supplementation can result in organ damage and may actually provide a growth advantage to pathogens.[24]  The RDA for adult males and postmenopausal females is 8 mg, and 18mg for menstruating adult females.  Heme iron is more readily absorbed than non-heme iron.  Heme iron is rich in lean meats and seafood, while non heme iron is found in nuts, beans, vegetables, and fortified grain products.[34]  Concomitantly consuming a source of vitamin C increases iron absorption.

Selenium

Deficiency in selenium can impair innate and adaptive immune responses, increase virulence of viral infections and increase cancer incidence.  While supplementation in deficient individuals may improve immune function, caution must be taken given the possible risk of worsening allergic asthma symptoms and decreasing the immune response against parasitic infections.[24]  The RDA for selenium is 55 mcg.  Dietary sources include Brazil nuts, seafoods, organ meats, muscle meats, cereals and other grains, and dairy products.[35]

Zinc

When there are disruptions in zinc metabolism, aspects of immune function are impaired including maturation and function of lymphocytes in the adaptive immune response, innate immune reactions such as phagocytosis and oxidative bursts and communication between components of the immune system through cytokines.[36]  Zinc also acts as an important regulator of the immune response and anti-inflammatory agent.  In chronic zinc deficiency, levels of proinflammatory cytokines increase leading to potential increased risk and severity of chronic inflammatory diseases (e.g., rheumatoid arthritis).[37]  Zinc acts as a gatekeeper of the immune system.  While deficiency can lead to overproduction of inflammatory molecules, atrophy of the thymus gland, disruption in the balance of T cells and decreased numbers of certain types of B cells, excess zinc can suppress the function of B and T cells and directly activate other inflammatory cells. [38]

Zinc deficiency has been linked to increased bacterial, viral, and fungal infections as well as increased atrophy of the thymus.  Supplementation with zinc has been shown to restore function of the thymus and improve immune function in the setting of gastrointestinal and respiratory tract infections, and reduce overactivity of cells types implicated in autoimmunity.[24]  The RDA for zinc is 11 mg for adult males and 8 mg for adult females. Oysters are especially rich in zinc, but red meat and poultry also offer zinc, in high amounts.  Other sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products.[39]

We are also discovering more and more that the impact of what we eat is not simply about the combination of micronutrients and macronutrients.  Our nutrition patterns, in addition to other lifestyle habits, greatly influence the environment of the digestive tract (which is the major interface between the external world and our internal environment) and the incredibly important mix of bacteria that reside there—the “microbiome.”  This microbiome has powerful influences on metabolism, disease risk, mood, and cognitive function.  The significance of the microbiome is illustrated in a study in which the transfer of a sample of a lean person’s intestinal bacteria to the gut of an individual with metabolic syndrome (a sort of prediabetic state) resulted in significant increase in insulin sensitivity of the receiver.[40]  Of note, the microbiome of the skin also increasingly is recognized as an important part of the health of skin and its immune system and of the pathology of skin diseases.[41]

The microbiome of the GI tract has a huge regulatory impact on our immune function—not only protecting us from illness-causing microbes but possibly also preventing the overactivity of the immune system seen in autoimmune diseases such as food allergies.  Disruptions in the gut microbiotia (“intestinal dysbiosis”) have been implicated in several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and myasthenia gravis.  While genetic and environmental factors certainly also play significant roles, certain gut bacteria patterns have been associated with these diseases and therapeutic interventions to shift those patterns have shown some improvement in disease expression. [42]

The balance of the human intestinal microbiome is influenced heavily during birth and in the newborn period.  The meconium of full-term newborns contains bacteria normally found in the maternal amniotic fluid, vaginal canal, and oral cavity.  Infants born via cesarean section have a different composition of their intestinal microbiome that bears more resemblance to skin bacteria.  Components of human breast milk act as prebiotics to help foster growth of healthy bacteria and antibiotics against pathogenic bacteria.  This combined with the fact that breast milk also contains 109 bacterial cells/L indicates how breastfeeding infants helps to support the growth of helpful bacteria such as Bifidobacterium spp. and Lactobacillus spp.  As the GI tract develops, the gut microbiome has significant impact on its maturation and on the training of the large portion of the immune system that resides in that GI tract.  The commensal bacteria help train the gut immune system to tolerate healthy bacteria, which prevents problematic chronic inflammation, and also stimulate the immune system at a low level to be able to recognize and fight pathogenic bacteria.  There also seems to be a window in early life in which the constitution of the gut microbiome influences overall stress responsiveness and anxiety. Supplementation with a probiotic may have a greater impact on immune function in older adults.[43]

Older adults are more susceptible to infections and cancer, which in turn are associated with a decrease in cellular immunity.  A meta-analysis of several small studies found that supplementation with a specific strain of bacteria (Bifidobacterium animalis ssp lactis HN019) improved markers of cellular immune function including enhanced natural killer cell tumoricidal activity and polymorphonuclear cell phagocytic capacity.[44]

Prebiotics are nondigestible food ingredients that help support good bacteria in the gut; examples include fructo-oligosaccharides, lactulose, lactitol and gluco-oligosaccharides.  Generally, they are not digested until they get to the large intestine.  Foods rich in prebiotics include honey, beer, onions, burdock root, asparagus, rye, Jerusalem artichokes, bananas, maple sugar, oats, and Chinese chives.[45]  The role of prebiotics supporting gut health through reducing pathogens and improving the balance of pro- and anti-inflammatory cytokines has mostly been studied indirectly by looking at how they support the growth of healthy bacteria, but more is being learned about their direct effects on gut health and immunity as well. [46]

Probiotics act directly on the health of the gastrointestinal tract by increasing the activity of natural killer cells and macrophages and influencing the secretion of immunoglobulins and cytokines.  They act indirectly by enhancing the gut epithelial barrier, altering mucus secretion and competitively excluding pathologic organisms. Different bacterial strains accomplish these influences via different mechanisms and knowing what type, when, and how much probiotic to supplement for any given disease state or cause of dysbiosis is an active area of study.[47]

What it takes to keep the gut healthy may vary based on the individual.  However, a few key components are rather common to all:

  • Avoidance of excess amount of inflammation, which can be caused by foods and medications that irritate the gut and/or lack of effective mechanisms to deal with life’s stresses
  • A healthy mucous layer, which lubricates the intestinal lining and feeds the healthy bacteria that reside there
  • An appropriate mix of healthy bacteria

For more information, refer to the “Irritable Bowel Syndrome (IBS)” Whole Health tool.

General principles around healthy eating were summarized well by Michael Pollan in his book In Defense of Food, in which he advised, “Eat food. Not too much. Mostly plants.”  Many of us may be looking for miracle foods that will boost immunity.  Coffee has been linked to lower levels of circulating chemokines and cytokines and increased diversity of the gut microbiota. [11]  Garlic has been shown to increase macrophage activity, natural killer cells and the production of B and T cells in addition to decreasing the number, duration, and severity of upper respiratory infections.  It appears to have antiviral actions against human rhinovirus, cytomegalovirus, herpes simplex, and influenza, in addition to antifungal and antiparasitic activity against organisms such as Candida albicans, Cryptosporidium, and Giardia.  In addition to in vitro studies, trials have used garlic powder and aged garlic extract to show decrease in upper respiratory infections.  As a whole food, garlic also acts as a prebiotic that helps support a healthy microbiome.[48]  In most cases, eating an anti-inflammatory diet can accomplish the adequate intake of the above micronutrients and foster a supportive environment for healthy gut bacteria.

Moderation of caloric intake also is important.  Studies have shown that undernutrition of macronutrients leads to more-frequent chronic infections but macronutrient excess has been associated with induction of inflammation and increased risk of chronic diseases such as diabetes and heart disease.[49]

Anti-inflammatory diets are generally high in fiber as well.  Diets higher in fiber have been shown to decrease colorectal cancer (CRC) incidence, and improve prognosis if CRC is diagnosed.  Gut bacteria can ferment insoluble fiber to produce short-chain fatty acids, which have beneficial effects on the gut immune system and protection against CRC.[11]

Traditional plant-based diets such as the Ancient Thali diet of India, heavily influenced by tenets of the Indian medicine Ayurveda, has been shown to be associated with lower rates of chronic disease such as type 2 diabetes and colon cancer.  This diet is low in processed foods, rich in prebiotic fiber and in plants and spices, which contain a wide variety of bioactive compounds that are anti-inflammatory in nature and help promote a healthy gut microbiome.  An example of these compounds is anthocyanins, a class of phytochemicals called polyphenols that are abundant in dark-colored fruits and vegetables such as berries, eggplants, and other red, purple, and blue produce.[50]  Flavonoids are another category of polyphenols.   A recent meta-analysis of 14 studies showed that supplementation with dietary flavonoids (0.2 to 1.2g/day) may decrease incidence of upper respiratory tract infections by 33% and decrease sick day counts by 40%. [51]

The balance between omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) in our diets is of particular importance.  The same enzymes in the body metabolize both, but the omega-6 fats promote inflammation while omega-3 fats promote wound healing and resolution of inflammation.[49]  Higher levels of marine-based omega-3 fatty acid intake has been shown to decrease recurrence and mortality rates in CRC.  This seems related to both the immune-modulating effects and beneficial impact on the gut microbiota of omega-3 fatty acids. [11]

Beneficial impact of omega-3 fatty acids on the arachidonic acid to EPA ratio in cell membranes may be greater in older adults. [43]

Addition of omega-3 fatty acids to parenteral nutrition given in the post-operative period of patients with gastrointestinal cancers results in a more favorable immune function profile and decreased risk of infective complications.[52]

The ideal ratio of intake of omega-6 and omega-3 fats seems to be around 2:1, but the standard American diet contains a ratio of something like 10:1 to 25:1—strongly tipping the balance toward inflammation.  In general, an anti-inflammatory diet includes the following foods:

  • Cold water fish, flax, and nuts
  • A wide variety of fruits and vegetables of various deep colors
  • Whole grains
  • Anti-inflammatory spices such as turmeric, ginger, rosemary, oregano, and cayenne

An anti-inflammatory diet avoids or limits the following foods:

  • Foods high in trans- and omega-6 fats (processed and red meats; dairy; partially hydrogenated oils; corn, cottonseed, grapeseed, peanut, and soy oils)
  • Refined carbohydrates (white breads, instant or white rice, rice and corn cereals, crackers, cookies, cake, etc.)
  • Soda and juices[53]

In animal models, poor parenteral nutrition patterns negatively affect immune function regardless of the diets of the offspring. [54]

A large number of herbal and nutritional supplements have been studied for their role in optimizing immune function.  The list and discussion on that topic is beyond the scope of this overview but is discussed in the “Adaptogens” Whole Health tool.

Never underestimate the power of diet when it comes to treating inflammation and bolstering the immune system.  The anti-inflammatory diet is one of the most popular tools used by integrative medicine practitioners.

Recharge

Numerous studies outline the relationship between sleep and immune function.  Many of these have found a correlation between changes in markers of innate immunity, such as interleukin 6 and tumor necrosis factor alpha levels, and sleep disruption. [55] Both sleep deprivation and acute illness (such as a viral infection) increase inflammatory markers that have been found to make us more tired.  Reciprocally, sleep deprivation leads to decreased immune function, leading to increased frequency of infections and decreased response to immunizations such as the influenza vaccine.  Increased levels of inflammation result from sleep deprivation, which may be the mechanism by which a chronically inadequate amount of sleep is associated with malignancy, heart disease, and stroke.

In contrast, sleep strengthens the immune response—most immune cells’ response to challenges (e.g., viral infections) peak at night.  These factors become a significant disadvantage for shift workers who have higher rates of gastrointestinal disease, cardiovascular disease, diabetes, metabolic syndrome, and cancers including prostate, colorectal, endometrial, and breast.[56]  Adequate sleep appears to be 7-8 hours per night.  Too much sleep (greater than 10 hours), however, has been associated with increased risk of cardiovascular disease.[57]  The body seems to have evolved with a basic sleep requirement for optimal immune function, and the importance of regular, adequate sleep should not be underestimated as it relates to both short-term immunity and long-term chronic disease risk.  Interventions such as tai chi and Cognitive Behavioral Therapy for Insomnia (CBT-I) have been found to improve sleep and lower inflammatory markers significantly compared to controls such as attending a sleep seminar.[55]  This speaks to the importance of active participation of the individual in improving their personal health outcomes.

Family, Friends, & Co-Workers

An interesting study took 90 newlywed couples and monitored several measures of immune function after a 30-minute discussion aimed at addressing and attempting to resolve 2-3 marital issues that pre-discussion questionnaires deemed to be the most likely to induce conflict.  Subjects, especially women, who showed more negative or hostile behaviors during the discussion were more likely to show decreases on several markers of immune function.[58]  How we perceive or handle stress and conflict can influence the physical function of our bodies.

Stresses such as marital disruption and caregiving for a relative with Alzheimer’s disease have been associated with both decreased in vitro function of immune cells and qualitative immune function changes such as frequency of herpes outbreaks.  There is some evidence to suggest that quality interpersonal relationships can be protective against these types of immune changes.[59]  Indeed, higher levels of social support have been shown to improve multiple aspects of immune function, including changes in CD4+ cell counts (a marker of HIV disease progression) in HIV-positive individuals.[60]

  • Personal relationships do not have to be limited to friends and family. David Rakel et al. performed an interesting study looking at the influence of a physician’s empathy on the outcomes of the common cold.  About 350 individuals were randomized to receive either: Standard care for cold symptoms in which the clinician took adequate history and performed appropriate physical exam, but avoided any attempt to connect with the patient or express empathy for their discomfort, or
  • “Enhanced” care in which the clinician strived to connect with the patient as an individual and offer compassion and empowerment to the patient for self-care.

Quantitative measures of immune response trended toward more robust, and symptom severity trended toward less severe in the enhanced group, but neither was statistically significant.  However, the duration of the illness was a full day less in those who felt a connection with or empathy from their clinician—this was statistically significant and comparable to the effects of the few antiviral medications that have been studied.[61]  The clinicians’ presence and compassion make a difference—human connection makes a difference.

Stress reduction should be a key component of any health plan where inflammation and supporting the immune system require attention.

Spirit & Soul and Power of the Mind

Individuals with higher levels of spiritual well-being, including participation in formal religion, seem to have better cardiovascular, neuroendocrine, and immune function.[62][63]  In our practice we frequently ask about spirituality, but we make sure that patients understand we are asking them how they define that.  Some helpful phrases that can start this conversation include the following:

  • “What do you feel connects you to things or people outside yourself?”
  • “What gives you a sense of meaning or purpose?”
  • “What makes you get out of bed in the morning?”

To help avoid people feeling like we are just asking about religion, we sometimes offer examples such as, “For some it is religion or meditation, but for others it is nature, music, the meaning of their work, art, being present with friends and family, volunteer work, etc.”

When our lives encounter a challenging time (e.g., stressed interpersonal relationships, illness in ourselves or in family members, etc.), our reactions to those situations can affect our resiliency and immune function.  For example, a review of 15 published trials showed eight that indicated psychotherapy improved cancer survival time and none showed an adverse effect.  While the mechanism of this result has yet to be elucidated, it is likely related to the relationship between stress and immune dysfunction, increase in inflammation, increase in stress hormones and/or changes in DNA and DNA expression related to these factors.[64]

Mindful awareness meditation has been studied extensively in relation to immune function.  This type of meditation is a practice that fosters an ability to take a step back and notice our reactions to external stimuli, giving us a chance to pause and choose how we will respond.  My favorite analogy to understand this was given by Katherine Bonus—former director of the University of Wisconsin Mindfulness-Based Stress Reduction Program.  She had a group of us look out a window at the street.  She told us to imagine just flinging ourselves on top of the next car that drove past—being carried away on top with no idea where it would take us or how fast or when it will turn.  This was a lot like how we might react to stress or pain—we see it coming and feel it is going to do something to us or cause us to feel a certain way, and we let it.  If we stop and observe exactly what it is, without expectation, we may have a bit of a decision point on how to respond differently.  Do I have to let that stress me out?  Is the pain really that bad, or am I expecting it to be?  And so on.

Some studies have shown mindful awareness to lead to more robust antibody response to the influenza vaccine.[65]  Others have failed to show this relationship but did correlate optimism, less anxiety, and lower perceived stress with high antibody levels post-immunization[66]  Mindful awareness meditation has been associated with decreased symptom severity in the common cold.[67]  Immune function profiles shifted from depressed to more normal profiles in patients with breast and prostate cancer after completion of an eight-week Mindfulness-Based Stress Reduction (MBSR) course.[68]  In women with breast cancer, mindful awareness has been shown to improve the cytotoxic activity of natural killer cells, which can be suppressed in the disease process.[69] A review of randomized control studies found that mindful awareness meditation decreased inflammation (as evidenced by decreased NF-kB transcription activity and CRP levels), increased cell-mediated immunity (as evidenced by increased CD4+ cell count/activity), and slowed biological aging (as evidenced by increased telomerase activity).[70]

Some believe meditative practices can positively impact cardiovascular health through the anti-inflammatory reflex.[71]  MBSR has been found to decrease markers of post-stress inflammation that may have implications for its use in chronic inflammatory conditions.[72]  Some evidence supports use of workplace-based mindful awareness programs as a means of decreasing inflammation as measured by decreases in CRP (a common marker of generalized inflammation), especially in nonobese individuals.[73]

Mechanisms by which mindful awareness impacts immune function likely have to do with the connection between emotional states, neurologic function, and the immune system.  This field of study, psychoneuroimmunology, is growing and seems to be scratching the surface of how our perception of the world impacts our physiology.   There appears to be a bidirectional relationship between the psychosocial impact on immune function and health of the immune system on resilience of an individual when confronted with both biologic and social challenges.[74] Mindful practices are not limited to meditation, however.  It is important to recognize that meditation may be counter to the belief systems of some individuals or simply not appealing to them.  Other examples of mindful practice are mindful walking, listening to music with two instruments and following just one, painting, working with one’s hands, and breathwork.  For more information, refer to the “Mindful Awareness” and “Power of the Mind” Whole Health tools.

Personal Health Plan

Name: Greg

Date: xx/xx/xxxx

Mission, Aspiration, Purpose (MAP):

My mission is to feel like a strong, healthy individual who is a good example of health for his children.

My Goals:

  • Quit smoking.
  • Improve ability to get to sleep.
  • Improve understanding and control of asthma.
  • Find ways to become less susceptible to frequent minor infections.
  • Increase fitness to the point of being able to participate in longer road bike races.
  • Find a healthy way to deal with the health problems of my brother and father.

Strengths (what’s going right already)/Challenges:

My Plan for Skill Building and Support

Mindful Awareness:

Areas of Self-Care:

  • Moving the Body
    • Progressively increase biking mileage after consulting with doctor about asthma. Get connected with a local bicycling club to help train for longer rides.
  • Surroundings
    • Continue smoke cessation.
    • Medically, make sure nothing is triggering asthma symptoms. Consult a doctor and together decide if there is an allergic component that would benefit from either medication or allergy testing. Think about the air quality at home and work and regularly change furnace filter or bring an air filter to the office.
    • Bring a few personal things into the office space to give the space a nicer feel.
    • Minimize unfinished reminders at home. Keep the workspace for current projects limited and organized. Reframe the next project as “possibility” rather than something stressful.
  • Food and Drink
    • Follow an anti-inflammatory diet to get more energy and help the immune system function at its peak. Decrease or cut out fast food and try to incorporate more fruits and vegetables—the more different colors, the better.
  • Recharge
    • Sit down with my wife, list all of the projects, and give a reasonable timeline—considering all other priorities. Make a to-do list and leave it outside the bedroom door the night before a busy day. Consider breathing exercises or a progressive muscle relaxation activity to help fall sleep.
  • Spirt and Soul and Power of the Mind
    • Start with things mentioned above and reflect on how they affect my overall sense of contentment by meditating or journaling. Commit to thinking of 2-3 things each day for which I am grateful—opportunities, relationships, material things, etc. Consider doing this as a family at the dinner table or with my kids when tucking them in.
  • Personal Development/Family, Friends, and Co-Workers
    • Reframe the way I think about work. In sales, easing that process for clients has the potential to make their day easier. There is a potential for purpose with every human interaction. Try to connect with co-workers once a month—attend a planned get-together or just strike up a conversation in the break room.
    • Carve time out each week to do an activity with my wife and children that is simply fun. Give everyone a turn in picking the activity—movie night, hiking, bowling, etc.
    • Read “Anticancer:  A New Way of Life,” by David Servan-Schreiber, an empowering book that may help me reflect on my personal cancer risk from my father.
    • Look into Al-Anon—a support group for people with friends and family with drinking problems—to support my brother. Offer support for his wife and children as well.
    • Volunteer at my children’s school to build a garden shed to give me something meaningful to do, while also getting to know others who may want to help.

Professional Care: Conventional and Complementary

  • Prevention/Screening
    • Meet with Primary Care Physician for complete review of health.
  • Treatment (e.g., conventional and complementary approaches, medications, and supplements)
    • VA medications
    • Astragalus 5-6 gm per day
      • Can help prevent the common cold and take seasonally as needed. Look for a label that has a USP or GMP seal to ensure a quality product.
    • Omega-3 fatty acids or fish oil 1,000 mg of DHA + EPA
      • Look for a product that is molecularly distilled to remove metals like mercury.
    • Skill building and education
      • Sleep hygiene
      • Nutrition
      • Foster a connection, sense of purpose, and gratitude

Referrals/Consults

  • Allergist

Community

Resources

  • Removing chemicals leaves less “stuff” for the immune system to deal with; visit the Environmental Working Group for more information.

My Support Team

  • Principal Professions
    • Primary Care Clinician
  • Personal
    • Wife

Next Steps

Please Note: This plan is for my personal use and does not comprise my complete medical or pharmacological data, nor does it replace my medical record.

Follow-Up With Greg

Through the process of completing his Personal Health Inventory (PHI), Greg realized that his life did not offer him the enjoyment he would like to have.  He felt sick all the time and was, to some degree, nervous about going forward with more exercise for fear of making his asthma worse.  He did not feel all that connected to anyone outside of his immediate family and had some significant stress with the health of his brother and father.  He seemed to want to do something with meaning, as his job was mostly a reliable source of income.  He desired to feel strong and healthy and be a good role model for his children.

Greg decided to start out by scheduling an appointment with his doctor to follow up regarding his asthma.  He wrote down a list of questions so that he would have a clear understanding of what he should expect from his treatment plan and how he could better manage it at home.  He also wanted to be clear on whether or not he had “restrictions” in terms of exercise.  He also decided to commit to giving up smoking and to ask for some help in developing a plan for that.  This became especially important as he realized its impact on his asthma and his worry given his father’s recent diagnosis of lung cancer.  Given the limited number of cigarettes he smoked, he was able to quit in about a month.  He felt he had a much better understanding of his asthma and knew when he needed to be seen due to symptoms.

Greg also decided get involved in his community a bit.  He felt volunteering to help his children’s school build a shed for their garden tools would be a good way to meet people.  It was a setting that felt more comfortable without the pressure of having to come up with conversation at a dinner party.  He even asked the other father who he knew was in bicycling club if he wanted to help on the project as well.  He eventually joined that biking group and was able to participate in the 112-mile bike ride after increasing his miles over about 2 years.

To help with his sleep, he decided to sit down with his wife and develop a time line of all the projects in the house that they want to get done.  They made sure it was over a long enough time frame and in small enough pieces that they could see progress without unreasonable expectations.  With that plan, he was able to feel like he could start working at a reasonable time, relax a bit, and not have his mind planning things when he was trying to sleep.

Author(s)

“Immune System Health” was written and updated by Greta Kuphal, MD (2014, updated 2020).

This Whole Health overview was made possible through a collaborative effort between the University of Wisconsin Integrative Health Program, VA Office of Patient Centered Care and Cultural Transformation, and Pacific Institute for Research and Evaluation.

References

  1. Helbert M. Immunology for Medical Students. In: Third ed.: Elsevier, Inc; 2017.
  2. Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol. 2005;78(4):819-835.
  3. Walsh NP, Gleeson M, Shephard RJ, et al. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev. 2011;17:6-63.
  4. Nieman DC. Exercise, upper respiratory tract infection, and the immune system. Med Sci Sports Exerc. 1994;26(2):128-139.
  5. Siedlik JA, Benedict SH, Landes EJ, Weir JP, Vardiman JP, Gallagher PM. Acute bouts of exercise induce a suppressive effect on lymphocyte proliferation in human subjects: A meta-analysis. Brain Behav Immun. 2016;56:343-351.
  6. Walsh NP, Oliver SJ. Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress. Immunol Cell Biol. 2016;94(2):132-139.
  7. Gunzer W, Konrad M, Pail E. Exercise-induced immunodepression in endurance athletes and nutritional intervention with carbohydrate, protein and fat-what is possible, what is not? Nutrients. 2012;4(9):1187-1212.
  8. Gleeson M, Walsh NP. The BASES expert statement on exercise, immunity, and infection. J Sports Sci. 2012;30(3):321-324.
  9. Woods JA, Vieira VJ, Keylock KT. Exercise, inflammation, and innate immunity. Immunol Allergy Clin North Am. 2009;29(2):381-393.
  10. Fairey AS, Courneya KS, Field CJ, Mackey JR. Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions. Cancer. 2002;94(2):539-551.
  11. Song M, Chan AT. The potential role of exercise and nutrition in harnessing the immune system to improve colorectal cancer survival. Gastroenterology. 2018;155(3):596-600.
  12. Khosravi N, Stoner L, Farajivafa V, Hanson ED. Exercise training, circulating cytokine levels and immune function in cancer survivors: A meta-analysis. Brain Behav Immun. 2019;81:92-104.
  13. Hojman P. Exercise protects from cancer through regulation of immune function and inflammation. Biochem Soc Trans. 2017;45(4):905-911.
  14. Wang CW, Ng SM, Ho RT, Ziea ET, Wong VC, Chan CL. The effect of qigong exercise on immunity and infections: a systematic review of controlled trials. Am J Chin Med. 2012;40(6):1143-1156.
  15. Ho RT, Wang CW, Ng SM, et al. The effect of t’ai chi exercise on immunity and infections: a systematic review of controlled trials. J Altern Complement Med. 2013;19(5):389-396.
  16. Kulkarni DD, Bera TK. Yogic exercises and health–a psycho-neuro immunological approach. Indian J Physiol Pharmacol. 2009;53(1):3-15.
  17. Falkenberg RI, Eising C, Peters ML. Yoga and immune system functioning: a systematic review of randomized controlled trials. J Behav Med. 2018;41(4):467-482.
  18. Crinnion WJ. Do environmental toxicants contribute to allergy and asthma? Altern Med Rev. 2012;17(1):6-18.
  19. Mukerjee D. Health impact of polychlorinated dibenzo-p-dioxins: a critical review. J Air Waste Manag Assoc. 1998;48(2):157-165.
  20. Kappos AD, Bruckmann P, Eikmann T, et al. Health effects of particles in ambient air. Int J Hyg Environ Health. 2004;207(4):399-407.
  21. Pedersen AF, Zachariae R, Bovbjerg DH. Psychological stress and antibody response to influenza vaccination: a meta-analysis. Brain Behav Immun. 2009;23(4):427-433.
  22. Nakata A. Psychosocial job stress and immunity: a systematic review. Methods Mol Biol. 2012;934:39-75.
  23. Haczku A, Panettieri RA, Jr. Social stress and asthma: the role of corticosteroid insensitivity. J Allergy Clin Immunol. 2010;125(3):550-558.
  24. Maggini S, Pierre A, Calder PC. Immune function and micronutrient requirements change over the life course. Nutrients. 2018;10(10).
  25. National Institutes of Health (Office of Dietary Supplements). Vitamin A. 2020; https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/. Accessed August 11, 2020.
  26. National Institutes of Health (Office of Dietary Supplements). Vitamin B6. 2020; https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/. Accessed August 11, 2020.
  27. Hernández A, Papadakos PJ, Torres A, et al. Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19. Rev Esp Anestesiol Reanim. 2020;67(5):245-252.
  28. National Institutes of Health (Office of Dietary Supplements). Vitamin C. 2020; https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/. Accessed August 11, 2020.
  29. Vanherwegen AS, Gysemans C, Mathieu C. Regulation of immune function by vitamin D and its use in diseases of immunity. Endocrinol Metab Clin North Am. 2017;46(4):1061-1094.
  30. Jiménez-Sousa M, Martínez I, Medrano LM, Fernández-Rodríguez A, Resino S. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease. Front Immunol. 2018;9:458.
  31. National Institutes of Health (Office of Dietary Supplements). Vitamin D. 2020; https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed August 11, 2020.
  32. National Institutes of Health (Office of Dietary Supplements). Vitamin E. 2020; https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. Accessed August 11, 2020.
  33. National Institutes of Health (Office of Dietary Supplements). Copper. 2020; https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/. Accessed August 11, 2020.
  34. National Institutes of Health (Office of Dietary Supplements). Iron. 2020; https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/. Accessed August 11, 2020.
  35. National Institutes of Health (Office of Dietary Supplements). Selenium. 2020; https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/. Accessed August 11, 2020.
  36. Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58-65.
  37. Bonaventura P, Benedetti G, Albarède F, Miossec P. Zinc and its role in immunity and inflammation. Autoimmun Rev. 2015;14(4):277-285.
  38. Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. 2017;9(12).
  39. National Institutes of Health (Office of Dietary Supplements). Zinc. 2020; https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/. Accessed August 11, 2020.
  40. Pollan M. Some of My Best Friends Are Germs. The New York Times Magazine. May 15, 2013. http://www.nytimes.com/2013/05/19/magazine/say-hello-to-the-100-trillion-bacteria-that-make-up-your-microbiome.html?pagewanted%3Dall&_r=1&. Accessed March 17, 2014.
  41. Egert M, Simmering R, Riedel CU. The association of the skin microbiota with health, immunity, and disease. Clin Pharmacol Ther. 2017;102(1):62-69.
  42. Rinaldi E, Consonni A, Guidesi E, Elli M, Mantegazza R, Baggi F. Gut microbiota and probiotics: novel immune system modulators in myasthenia gravis? Ann N Y Acad Sci. 2018;1413(1):49-58.
  43. Yaqoob P. Ageing alters the impact of nutrition on immune function. Proc Nutr Soc. 2017;76(3):347-351.
  44. Miller LE, Lehtoranta L, Lehtinen MJ. The effect of bifidobacterium animalis ssp. lactis HN019 on cellular immune function in healthy elderly subjects: systematic review and meta-analysis. Nutrients. 2017;9(3).
  45. Rindfleisch A. Probiotics and prebiotics: frequently asked questions 2008. https://www.fammed.wisc.edu/files/webfm-uploads/documents/outreach/im/handout_probiotics_patient.pdf. Accessed August 11, 2020.
  46. Shokryazdan P, Faseleh Jahromi M, Navidshad B, Liang JB. Effects of prebiotics on immune system and cytokine expression. Med Microbiol Immunol. 2017;206(1):1-9.
  47. La Fata G, Weber P, Mohajeri MH. Probiotics and the gut immune system: indirect regulation. Probiotics Antimicrob Proteins. 2018;10(1):11-21.
  48. Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr. 2016;146(2):389s-396s.
  49. Afacan NJ, Fjell CD, Hancock RE. A systems biology approach to nutritional immunology – focus on innate immunity. Mol Aspects Med. 2012;33(1):14-25.
  50. Shondelmyer K, Knight R, Sanivarapu A, Ogino S, Vanamala JKP. Ancient Thali diet: gut microbiota, immunity, and health. Yale J Biol Med. 2018;91(2):177-184.
  51. Somerville VS, Braakhuis AJ, Hopkins WG. Effect of flavonoids on upper respiratory tract infections and immune function: a systematic review and meta-analysis. Adv Nutr. 2016;7(3):488-497.
  52. Zhao Y, Wang C. Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China. Medicine. 2018;97(16):e0472.
  53. Kohatsu W. The Anti Inflammatory Diet. In: Rakel D, ed. Integrative Medicine. 3rd ed. Philadelphia, PA: Saunders, an imprint of Elsevier, Inc; 2012:795-802.
  54. Grueber CE, Gray LJ, Morris KM, Simpson SJ, Senior AM. Intergenerational effects of nutrition on immunity: a systematic review and meta-analysis. Biol Rev Camb Philos Soc. 2018;93(2):1108-1124.
  55. Irwin MR, Opp MR. Sleep health: Reciprocal regulation of sleep and innate immunity. Neuropsychopharmacology. 2017;42(1):129-155.
  56. Gamaldo CE, Shaikh AK, McArthur JC. The sleep-immunity relationship. Neurol Clin. 2012;30(4):1313-1343.
  57. Ganz FD. Sleep and immune function. Crit Care Nurse. 2012;32(2):e19-e25.
  58. Kiecolt-Glaser JK, Malarkey WB, Chee M, et al. Negative behavior during marital conflict is associated with immunological down-regulation. Psychosom Med. 1993;55(5):395-409.
  59. Kennedy S, Kiecolt-Glaser JK, Glaser R. Immunological consequences of acute and chronic stressors: mediating role of interpersonal relationships. Br J Med Psychol. 1988;61 ( Pt 1):77-85.
  60. Uchino BN, Cacioppo JT, Kiecolt-Glaser JK. The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychol Bull. 1996;119(3):488-531.
  61. Rakel DP, Hoeft TJ, Barrett BP, Chewning BA, Craig BM, Niu M. Practitioner empathy and the duration of the common cold. Fam Med. 2009;41(7):494-501.
  62. Seeman TE, Dubin LF, Seeman M. Religiosity/spirituality and health. A critical review of the evidence for biological pathways. Am Psychol. 2003;58(1):53-63.
  63. Townsend M, Kladder V, Ayele H, Mulligan T. Systematic review of clinical trials examining the effects of religion on health. South Med J. 2002;95(12):1429-1434.
  64. Spiegel D. Minding the body: Psychotherapy and cancer survival. Br J Health Psychol. 2013.
  65. Davidson RJ, Kabat-Zinn J, Schumacher J, et al. Alterations in brain and immune function produced by mindfulness meditation. Psychosom Med. 2003;65(4):564-570.
  66. Hayney MS, Coe CL, Muller D, et al. Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial. Hum Vaccin Immunother. 2014;10(1):83-91.
  67. Barrett B, Hayney MS, Muller D, et al. Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial. Ann Fam Med. 2012;10(4):337-346.
  68. Carlson LE, Speca M, Patel KD, Goodey E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosom Med. 2003;65(4):571-581.
  69. Abrahão CA, Bomfim E, Lopes-Júnior LC, Pereira-da-Silva G. Complementary therapies as a strategy to reduce stress and stimulate immunity of women with breast cancer. J Evid Based Integr Med. 2019;24:2515690×19834169.
  70. Black DS, Slavich GM. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Ann N Y Acad Sci. 2016;1373(1):13-24.
  71. Olex S, Newberg A, Figueredo VM. Meditation: should a cardiologist care? Int J Cardiol. 2013;168(3):1805-1810.
  72. 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;27(1):174-184.
  73. Malarkey WB, Jarjoura D, Klatt M. Workplace based mindfulness practice and inflammation: a randomized trial. Brain Behav Immun. 2013;27(1):145-154.
  74. Dantzer R, Cohen S, Russo SJ, Dinan TG. Resilience and immunity. Brain Behav Immun. 2018;74:28-42.

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