Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements

Immunosuppression in athletes involved in heavy training is undoubtedly multifactorial in origin. Training and competitive surroundings may increase the athlete's exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. Although it is impossible to counter the effects of all of the factors that contribute to exercise-induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by eating a well-balanced diet that includes adequate protein and carbohydrate, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. Consuming carbohydrate (but not glutamine or other amino acids) during exercise attenuates rises in stress hormones, such as cortisol, and appears to limit the degree of exercise-induced immunosuppression, at least for non-fatiguing bouts of exercise. Evidence that high doses of anti-oxidant vitamins can prevent exercise-induced immunosuppression is also lacking.     

Nutrition Facts in Multiple Sclerosis

The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.     

The role of nutrition in viral disease

Malnutrition has been associated with a decrease in immune function. Impairment of immune function may lead to increased susceptibility to infection with viruses. Although there are many studies documenting the effect of host nutritional status on immune functions, fewer studies have examined the effect of host nutritional status on viral pathogenesis. This review examines the relationship between viral infection and the nutritional status of the host, and documents that not only can the nutritional status of the host affect immune function, but can have profound effects on the virus itself. One mechanism by which nutritional status affects the virulence of the viral pathogen involves selection for virulent viral genotypes. Other mechanisms remain to be elucidated.     

Antioxidants and vision health: facts and fiction

A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.     

Investment in Constitutive Immune Function by North American Elk Experimentally Maintained at Two Different Population Densities

Natural selection favors individuals that respond with effective and appropriate immune responses to macro or microparasites. Animals living in populations close to ecological carrying capacity experience increased intraspecific competition, and as a result are often in poor nutritional condition. Nutritional condition, in turn, affects the amount of endogenous resources that are available for investment in immune function. Our objective was to understand the relationship between immune function and density dependence mediated by trade-offs between immune function, nutritional condition, and reproduction. To determine how immune function relates to density-dependent processes, we quantified bacteria killing ability, hemolytic-complement activity, and nutritional condition of North American elk (Cervus elaphus) from populations maintained at experimentally high- and low-population densities. When compared with elk from the low-density population, those from the high-density population had higher bacteria killing ability and hemolytic-complement activity despite their lower nutritional condition. Similarly, when compared with adults, yearlings had higher bacteria killing ability, higher hemolytic-complement activity, and lower nutritional condition. Pregnancy status and lactational status did not change either measure of constitutive immunity. Density-dependent processes affected both nutritional condition and investment in constitutive immune function. Although the mechanism for how density affects immunity is ambiguous, we hypothesize two possibilities: (i) individuals in higher population densities and in poorer nutritional condition invested more into constitutive immune defenses, or (ii) had higher parasite loads causing higher induced immune responses. Those explanations are not mutually exclusive, and might be synergistic, but overall our results provide stronger support for the hypothesis that animals in poorer nutritional condition invest more in constitutive immune defenses then animals in better nutritional condition. This intriguing hypothesis should be investigated further within the larger framework of the cost and benefit structure of immune responses.     

Nutritional status, genetic susceptibility, and insulin resistance--important precedents to atherosclerosis

Atherosclerosis is a progressive disease that starts early in life and is manifested clinically as coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease. CAD remains the leading cause of morbidity and mortality in Western society despite the great advances made in understanding its underlying pathophysiology. The key risk factors associated with CAD include hypercholesterolemia, hypertension, poor diet, obesity, age, male gender, smoking, and physical inactivity. Genetics also play an important role that may interact with environmental factors, including diet, nutritional status, and physiological parameters. Furthermore, certain chronic inflammatory conditions also predispose to the development of CAD. The spiraling increase in obesity rates worldwide has made it more pertinent than ever before to understand the metabolic perturbations that link over nutrition to enhanced cardiovascular risk. Great breakthroughs have been made at the pharmacological level to manage CAD; statins and aspirin have revolutionized treatment of CAD and prolonged lifespan. Nonetheless, lifestyle intervention prior to clinical presentation of CAD symptoms would negate/delay the need for chronic pharmacotherapy in at-risk individuals which in turn would relieve healthcare systems of a costly burden. Throughout this review, we debate the relative impact of nutrition versus genetics in driving CAD. We will investigate how overnutrition affects adipose tissue biology and drives IR and will discuss the subsequent implications for the cardiovascular system. Furthermore, we will discuss how lifestyle interventions including diet modification and weight loss can improve both IR and metabolic dyslipidemia that is associated with obesity. We will conclude by delving into the concept that nutritional status interacts with genetic susceptibility, such that perhaps a more personalized nutrition approach may be more effective in determining diet-related risk as well as response to nutritional interventions.     

Exercise‐stimulated interleukin‐15 is controlled by AMPK and regulates skin metabolism and aging

Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle‐to‐skin signaling occurs. We demonstrate that endurance exercise attenuates age‐associated changes to skin in humans and mice and identify exercise‐induced IL‐15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL‐15 expression in part through skeletal muscle AMP‐activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL‐15 therapy mimics some of the anti‐aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low‐dose IL‐15 therapy may prove to be a beneficial strategy to attenuate skin aging.     

Importance of exercise immunology in health promotion

Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. The effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. In this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation.     

Infection,inflammation and exercise in cystic fibrosis

Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF).Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health.In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF.     

Effects of exercise on immune functions of undernourished mice.

Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response.     

Nutritional status and immune functions in maintenance hemodialysis patients

Epidemiological studies suggest various kinds of immune dysregulation in hemodialysis (HD) patients. The aim of this study was to investigate the relationship between immune functions and nutritional status of HD patients. We studied 54 patients with ESRD on chronic HD, included 34 females and 20 males with mean age 46.6 +/- 16.3 (18-77) years. We measured the height and dry weight of all patients. The BMI was calculated by dividing weight (kg) by height squared (m(2)). In all patients serum urea, creatinine, albumin, iron, cholesterol, triglyceride, CRP, IgG, IgM, IgA, CD4, CD8, CD19, CD16-56 lymphocytes were measured. Kt/V values were calculated according to DOQI guideline. In this study, a positive correlation between albumin, cholesterol, and triglyceride levels as nutritional parameters and immune functions in terms of total and subtype lymphocyte counts was observed. Further prospective studies are needed to determine the clinical importance of this finding and the appropriate means of measurement and effects of nutrition on immune function in hemodialysis patients.     

Exercise‐linked improvement in age‐associated loss of balance is associated with increased vestibular input to motor neurons

Age‐associated loss of muscle function is exacerbated by a concomitant reduction in balance, leading to gait abnormalities and falls. Even though balance defects can be mitigated by exercise, the underlying neural mechanisms are unknown. We now have investigated components of the proprioceptive and vestibular systems in specific motor neuron pools in sedentary and trained old mice, respectively. We observed a strong age‐linked deterioration in both circuits, with a mitigating effect of exercise on vestibular synapse numbers on motor neurons, closely associated with an improvement in gait and balance in old mice. Our results thus describe how the proprioceptive and vestibular systems are modulated by age and exercise, and how these changes affect their input to motor neurons. These findings not only make a strong case for exercise‐based interventions in elderly individuals to improve balance, but could also lead to targeted therapeutic interventions aimed at the respective neuronal circuitry.     

Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging.     

Anticoagulación en población anciana con fibrilación auricular no valvular. Artículo de revisión

Aging is an important risk factor for patients with atrial fibrillation. The estimated prevalence of atrial fibrillation in patients aged ≥80 years is 9–10%, and is associated with a four to five fold increased risk of embolic stroke, and with an estimated increased stroke risk of 1.45-fold per decade in aging. Older age is also associated with an increased risk of major bleeding with oral anticoagulant therapy. This review will focus on the role of oral anticoagulation with new oral anticoagulants, non-vitamin K antagonist in populations with common comorbid conditions, including age, chronic kidney disease, coronary artery disease, on multiple medication, and frailty. In patients 75 years and older, randomised trials have shown new oral anticoagulants to be as effective as warfarin, or in some cases superior, with an overall better safety profile, consistently reducing rates of intracranial haemorrhages. Prior to considering oral anticoagulant therapy in an elderly frail patient, a comprehensive assessment should be performed to include the risks and benefits, stroke risk, baseline kidney function, cognitive status, mobility and fall risk, multiple medication, nutritional status assessment, and life expectancy.     

The immune responses to diabetes in BB rats supplemented with vitamin A

A substantial amount of evidence suggests that in type I diabetes, vitamin A and zinc status could be of concern because of their impaired metabolic availability. Because both vitamin A and zinc play important roles in the regulation of immune function, the present study was undertaken to examine the immune responses to vitamin A and zinc supplements in diabetic-prone Bio-Breed rats (BBdp), and if the supplements increase the incidence of diabetes. Weanling BBdp rats were fed a NIH-07 diet supplemented with vitamin A either alone or in combination with zinc up to 120 days of age. A greater percentage of rats developing diabetes was found in rats that had supplements of vitamin A and zinc (67%) than those on the basal diet (55%) or with vitamin A supplementation alone (50%). The B cells and macrophages were all markedly increased, whereas CD(4)(+) and CD(8)(+) T cells were decreased at the onset of diabetes. However, this immune status was not changed by vitamin A and zinc supplements. The plasma vitamin A levels were significantly decreased in the presence of diabetes and the vitamin A status did not improve when the rats were given vitamin A and zinc supplements. The Natural Killer cell cytotoxicity on a per-cell basis was significantly decreased in the presence of diabetes, irrespective of supplements with vitamin A and zinc. Overall, results indicated that vitamin A and immune status are both affected by type I diabetes; these effects, however, are not responsive to supplemental intakes of vitamin A either alone or in combination with zinc.     

Association between Functional Capacity Decline and Nutritional Status Based on the Nutrition Screening Initiative Checklist: A 2-Year Cohort Study of Japanese Community-Dwelling Elderly

AimTo assess whether nutritional status based on the Nutrition Screening Initiative Checklist is useful for predicting functional capacity decline in community-dwelling Japanese elderly.MethodsThis two-year observational cohort study included 536 community-dwelling Japanese (65 years and older at baseline) who were independent in both activities and instrumental activities of daily living. Demographic attributes, chronic illness, lifestyle-related habits, nutritional status, functional capacity, and anthropometric measurements were assessed, with decline in functional capacity used as the outcome measure.ResultsSubjects were classified into three groups as follows based on the Nutrition Screening Initiative Checklist: low (59.5%), moderate (23.7%), and high (16.8%) nutritional risk. Significant differences were found between nutritional status and the following four baseline variables: age, hypertension, cerebrovascular diseases, and current smoking. However, no significant differences were evident between nutritional status and sex, body mass index, diabetes, drinking habit, or exercise habit. Logistic regression analysis adjusted for age, sex, body mass index, hypertension, cerebrovascular diseases and smoking habit showed that the high nutritional risk group was significantly associated with a decline in both activities of daily living (odds ratio: 4.96; 95% confidence interval (CI): 1.59–15.50) and instrumental activities of daily living (OR: 2.58; 95% CI: 1.31–5.06) compared with the low nutritional risk group.ConclusionsPoor nutritional status based on the Nutrition Screening Initiative Checklist was associated with a decline in functional capacity over a 2-year period in community-dwelling Japanese elderly. These results suggest that the Nutrition Screening Initiative Checklist is a suitable tool for predicting functional capacity decline in community-dwelling elderly.     

Cognitive impairment and mortality in a cohort of elderly people.

OBJECTIVES--To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over. DESIGN-A 20 year follow up study of a cohort of randomly selected elderly people living in the community who in 1973-4 had taken part in a nutritional survey funded by the Department of Health and Social Security. SETTING--Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS--921 men and women whose cognitive function was assessed by a geriatrician in 1973-4 and for whom data on health, socioeconomic circumstances, and diet had been recorded. RESULTS--Cognitive impairment was associated with increased mortality, in particular death from ischaemic stroke. Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 (95% confidence interval 1.4 to 5.5), compared with those who gained the maximum score (10), after adjustment for age, sex, blood pressure, serum cholesterol concentration, and vitamin C intake. These associations were independent of illness or social class. At the time of the nutritional survey, cognitive function was poorest in those with the lowest vitamin C status, whether measured by dietary intake or plasma ascorbic acid concentration. The relation between vitamin C status and cognitive function was independent of age, illness, social class, or other dietary variables. CONCLUSION--The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function. Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis. A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease.     

Special feature for the Olympics: effects of exercise on the immune system: exercise effects on mucosal immunity

The present review examines the effects of exercise on mucosal immunity in recreational and elite athletes and the role of mucosal immunity in respiratory illness. Habitual exercise at an intense level can cause suppression of mucosal immune parameters, while moderate exercise may have positive effects. Saliva is the most commonly used secretion for measurement of secretory antibodies in the assessment of mucosal immune status. Salivary IgA and IgM concentrations decline immediately after a bout of intense exercise, but usually recover within 24 h. Training at an intense level over many years can result in a chronic suppression of salivary immunoglobulin levels. The degree of immune suppression and the recovery rates after exercise are associated with the intensity of exercise and the duration or volume of the training. Low levels of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an increased risk of respiratory illness in athletes. Monitoring mucosal immune parameters during critical periods of training provides an assessment of the upper respiratory tract illness risk status of an individual athlete. The mechanisms underlying the mucosal immune suppression are unknown.     

Sex‐specific life history responses to nymphal diet quality and immune status in a field cricket

Individual fitness is expected to benefit from earlier maturation at a larger body size and higher body condition. However, poor nutritional quality or high prevalence of disease make this difficult because individuals either cannot acquire sufficient resources or must divert resources to other fitness‐related traits such as immunity. Under such conditions, individuals are expected to mature later at a smaller body size and in poorer body condition. Moreover, the juvenile environment can also produce longer‐term effects on adult fitness by causing shifts in resource allocation strategies that could alter investment in immune function and affect adult lifespan. We manipulated diet quality and immune status of juvenile Texas field crickets, Gryllus texensis, to investigate how poor developmental conditions affect sex‐specific investment in fitness‐related traits. As predicted, a poor juvenile diet was related to smaller mass and body size at eclosion in both sexes. However, our results also reveal sexually dimorphic responses to different facets of the rearing environment: female life history decisions are affected more by diet quality, whereas males are affected more by immune status. We suggest that females respond to decreased nutritional income because this threatens their ability to achieve a large adult body size, whereas male fitness is more dependent on reaching adulthood and so they invest in immunity and survival to eclosion.     

Exercise and humoral mediators of peripheral energy balance: ghrelin and adiponectin

Ghrelin and adiponectin are recently discovered peptides that are both associated with energy homeostasis and insulin action. In addition, circulating levels of both peptides are altered in obese populations and are associated with poor health. Moreover, expression of ghrelin and adiponectin returns to normal levels following weight loss in obese patients. Because exercise training improves the health status of obese individuals and is associated with reduction of body weight, there is interest in the effects of exercise on adiponectin and ghrelin and whether these peptides may provide better understanding of how exercise improves health. Ghrelin levels do not increase in response to acute running and cycling in humans, and therefore ghrelin does not appear to regulate growth hormone (GH) release during exercise. There is some evidence that ghrelin levels are suppressed following resistance exercise of moderate intensity and are lower with higher GH concentrations during aerobic exercise. It has been suggested that negative feedback from elevated GH produces the reductions, but why these responses have not been consistently found in other studies and whether postexercise reduction in ghrelin affects appetite warrants further investigation. There are a few studies (but not all) that suggest long-term chronic exercise produces increases in ghrelin levels when weight loss is produced. Ghrelin levels are much higher in amenorrheic athletes than in ovulating exercisers or in female exercisers with a luteal phase defect, suggesting an association with reproductive function. Adiponectin concentrations do not change in response to moderate and strenuous running or low- and moderate- intensity cycling. Most studies have revealed that chronic exercise that improves fitness levels, increases insulin sensitivity, and reduces body weight, will increase resting adiponectin levels. However, it does not appear that changes in insulin sensitivity brought about by moderate exercise training are attributable to adiponectin.