NIHR Southampton Biomedical Research Centre in nutrition Nutrition and immune system in exercise: a 2017 consensus statement Philip Calder Professor of Nutritional Immunology University of Southampton (pcc@soton.ac.uk) PENSA, November 2017 The NIHR Southampton Biomedical Research Centre in nutrition is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospital Southampton NHS Foundation Trust and the University of Southampton
Exercise Immunology Reviews (2017) 23, 8-50
Why? Good nutrition is important in supporting the immune system Exercise is a challenge to the immune system Nutritional immunomodulation in the context of exercise is a new but growing field Global sports nutrition is growing Elite athletes have a high level of expectation from nutritional strategies Elite athletes are exposed to many factors that impair the immune response (exhausting training, long travel, sleep disturbances, psychological stress) nutrition could help to mitigate this Elderly, overweight and ill patients are often prescribed physical training programmes nutrition could be supportive of these
What is covered? Carbohydrates Fatty acids Branched chain amino acids Glutamine Polyphenols Herbal supplements Antioxidants Minerals Probiotics and prebiotics Vitamin D Bovine colostrum Competitive athletes Military Overweight and obese Elderly Biomarkers
The immune system. is a cell and tissue system that protects the individual from invading pathogens
A well functioning immune system is key to providing robust defence against pathogenic organisms
Appropriate nutrient supply Appropriate nutrient status (& stores) Appropriate immune function Defence against pathogens
INADEQUATE nutrient supply INADEQUATE nutrient status (& stores) IMPAIRED immune function IMPAIRED defence against pathogens
Heavy training/endurance events increase susceptibility to infection
Breathing rate & depth Type of breathing Gut permeability Infections Immune impairment Close contact with other persons Physical contact/ abrasions
EXPOSURE Breathing rate & depth Type of breathing Gut permeability Infections DEFENCE Immune impairment Close contact with other persons Physical contact/ abrasions
Acute effects of exercise on immunity Circulating immune cell numbers and functions are temporarily altered following a prolonged bout of heavy exercise Increased numbers of leukocytes in the bloodstream (neutrophils & monocytes but fewer lymphocytes & NK cells) Increased plasma concentrations of inflammatory cytokines (TNF, IL-1, IL-6), anti-inflammatory cytokines (IL-1ra, IL-10) and positive acute phase proteins Decreased functional responses of neutrophils, NK cells, APCs, T cells, B cells etc.
Acute exercise: Circulating leukocytes 2.5 to 3 hours of intensive running (n = 62 marathon runners) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
Acute exercise: Phagocytosis and oxidative burst Granulocytes Monocytes 2.5 hours of intensive running (n = 30 marathon runners) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
Acute exercise: NK cell activity Impairment may last for days 2.5 hours of intensive running (n = 62 marathon runners & n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
# of NK cells drops => decreased activity mirrors the fall in number (activity per NK cell not altered?) Impairment may last for days 2.5 hours of intensive running (n = 62 marathon runners & n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
Acute exercise: T cell proliferation May reflect decreased circulating # of T cells 2.5 hours of intensive running (n = 22 marathon runners vs. n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
Decreased APC function Fewer T cells Decreased T cell function
Acute exercise: DTH response Triatheletes (A) vs. non-exercising triathletes (B) vs. moderately trained individuals (C) DTH administered at the end of the event Scored 2.5 days later Bruunsgaard et al. (1997) Med Sci Sports Exerc 29, 1176-1181
Acute exercise: Inflammatory cytokines NOTE: Less effect on TNF and IL-1 NOTE: Smaller effect with shorter duration and less intense exercise NOTE: Different cytokines likely to show different temporal changes 2.5 hours of intensive running (n = 30 marathon runners) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
Pedersen et al. (2001) Exercise Immunol Rev 7, 18-31
Acute exercise: Secretory IgA Nasal IgA decreased by up to 70% for up to 18 hr after a 31 km run Salivary IgA declined following 2 to 3 hr of exhaustive ski competition in elite crosscountry skiers Salivary IgA declined after 2 hr of hard exercise in cyclists Low salivary IgA preceded URTI in elite squash and hockey players
Summary of the acute effects of intensive exercise on the immune system Neutrophilia and lymphopenia Increased (blood) neutrophil and monocyte phagocytosis Decreased NK cell activity Decreased T cell response Decreased APC function Decreased secretory IgA Decreased DTH response Maintained humoral responses (B cell driven) Increased circulating pro- and anti-inflammatory cytokines
Acute exercise: Stress hormones 2.5 hours of intensive running (n = 22 marathon runners vs. n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82, 1385-1394
STRESS Physical Psychological Emotional Sleep deprivation Nutritional Stress hormones (cortisol, adrenaline etc.) Impaired cell mediated immunity Other factors (exposure) Increased risk of infection
Pre-exercise Elite swimmers 7 month training season Immune parameters measured monthly pre and post exercise Post-exercise Gleeson et al. (1995) Clin Exp Immunol 102, 210-216
TRAINING & COMPETITION STRESS Physical Psychological Emotional Sleep deprivation Nutritional Stress hormones (cortisol, adrenaline etc.) Impaired cell mediated immunity Other factors (exposure) Increased risk of infection
TRAINING & COMPETITION STRESS Physical Psychological Emotional Sleep deprivation Nutritional TARGETS FOR INTERVENTION Stress hormones (cortisol, adrenaline etc.) Impaired cell mediated immunity Other factors (exposure) Increased risk of infection
TRAINING & COMPETITION STRESS Physical Psychological Emotional Sleep deprivation Nutritional TARGETS FOR INTERVENTION Stress hormones (cortisol, adrenaline etc.) Impaired cell mediated immunity Other factors (exposure) Increased risk of infection
Nutrition?
Poor nutritional state can arise through practices associated with training & competition Weight loss regimens Weight maintenance regimens Lack of appreciation of diet/lack of time due to focus on training/competition Unusual dietary practices Increased losses through sweat Reliance on supplements Use of high dose supplements
Appropriate nutrient supply Appropriate nutrient status (& stores) Appropriate immune function Defence against pathogens
INADEQUATE nutrient supply INADEQUATE nutrient status (& stores) IMPAIRED immune function IMPAIRED defence against pathogens
Carbohydrates Rationale: limit stress => stress hormones => better maintenance of immunity Prolonged exercise over several days + low CHO diet => increased stress hormone and cytokine responses to exercise Consumption of CHO during exercise limits the rise in stress hormones and cytokines and limits the effects of exercise on circulating leukocyte numbers, neutrophil function and T cell function CHO consumption during exercise has limited effect on NK cell function and salivary IgA One study reported a trend towards lower URTI in marathon runners who consumed extra CHO during the race can be considered as a partial countermeasure for exercise-induced immunesuppression
Omega-3 fatty acids ( Fish oils ) Rationale: anti-inflammatory; wide-ranging health benefits; beneficial post-surgery and in critical illness Little explored in the context of exercise High doses may be immunosuppressive and may induce oxidative stress Possibly some effects on markers of inflammation and immunity in elite swimmers In elite cyclists 2.4 g/day omega-3 for 6 weeks did not alter exercise-induced increases in plasma cytokines, blood total leukocytes, serum C-reactive protein or the decrease in the salivary IgA In untrained athletes omega-3 decrease muscle soreness caused by exercise Overall difficult to interpret : better studies needed
Glutamine Rationale: fuel for immune cells; maintains optimal immune function in vitro; beneficial in post-surgery, burns and critical illness; blood concentration declines with exercise Limited effect on exercise-induced alterations in immune function when consumed during or after exercise One study reported lower URTI in marathon runners who consumed glutamine more studies need to investigate the apparent link between glutamine and the decreased incidence of self-reported URTI
Branched-chain amino acids Rationale: Energy source; precursor to glutamine Concentration decreases during exercise Prevented exercise-induced decline in plasma glutamine Chronic pre-endurance race consumption prevented the decline in T cell function Work via glutamine or is there another mechanism of action? evidence is weak
Quercetin Rationale: a plant polyphenol with antioxidant and anti-inflammatory effects (in vitro) In cyclists 1 g/day (typical intake from diet 10-100 mg/day) for 3 weeks decreased (by 85%) post-exercise URTI [but - high rate of URTI in control group] but there was NO effect on any immune parameter measured In cyclists quercetin in combination with other polyphenols and omega-3 fatty acids partially countered post-exercise inflammation
Antioxidant vitamins Rationale: Oxidative stress is immunosuppressive and pro-inflammatory; thus antioxidants may decrease inflammation and improve cell-mediated immunity High doses of vitamin C (0.5 to 1 g/day) decreased incidence of URTI in ultramarathon runners Vitamin C (500 mg/day) + Vitamin E (400 IU/day) decreased exercise-induced rise in cortisol and IL-6 and maintained neutrophil function But antioxidant supplementation mitigates important exercise-induced adaptations (i.e. oxidative stress may have some benefits)
Zinc Rationale: Essential for immune function; component of antioxidant defence system (SOD); lost in sweat Limited evaluation in the context of exercise High doses impair immune function: exerciseinduced reduction in T cell function exaggerated by 50 mg Zn + 3 mg Cu/day for 6 days no evidence showing that supplementing nondeficient athletes might boost the immune system or prevent exercise-induced immunodepression
Probiotics Rationale: live bacteria that interact with host gut epithelia and immune system -> anti-inflammatory and immune enhancing; improve immune function and decrease infection in other settings In elite distance runners L. fermentum for 28 days decreased risk and severity of respiratory illness and enhanced some immune parameters L. acidophilus for one month prevented exerciseinduced impairment of T cell function L. casei for one month partly prevented exerciseinduced decline in NK cell activity L. rhamnosus GG for 3 months reduced the duration of GI-symptoms during marathon training and in the 2 weeks following a marathon L. casei did NOT affect immune changes or URTI during commando training L. casei maintained salivary IgA and lowered incidence of URTI over 4 months in university athletes the same benefits [lower risk or URTI] seem to exist in athletic populations
Vitamin D Rationale: promotes anti-microbial immunity in vitro and in model systems; many individuals have low vitamin D status Shown to reduce URTI in some studies (non athletes) Little explored so far Beware high dose supplementation
Bovine colostrum Rationale: antibacterial, anti-viral, anti-inflammatory; important in early immune development (in calves!) Several studies report less self-reported URTI in those supplemented with bovine colostrum for more than 4 weeks effect of illness duration is less conclusive
Summary #1 The immune system is complex Intensive exercise has well documented effects on stress hormones, blood immune cells, plasma cytokines, APC, T and NK cell function, secretory IgA -> generally speaking causes transient immunosuppression Intensive exercise can increase risk of URTI (immune effects one factor involved) Nutrition is important to maintaining optimal immune function Poor nutrition is likely to induce sub-optimal immune function and is not likely to provide the best buffer to the effects of exercise
Summary #2 Many nutritional approaches have been considered in order to influence immune outcomes in athletes, but many of these approaches have been poorly explored to date CHO effect is the best described -> less stress, better immune function and less URTI There is some supportive evidence for BCAA and probiotics There is less (or less clear) evidence for zinc, omega-3 fats, quercetin and other polyphenols, and prebiotics and these should be explored further The early potential of glutamine has not been borne out Healthy eating approaches should be encouraged