Nutrition and immunity: perspectives on key issues and next steps.

In January 2022, a group of experts came together to discuss current perspectives and future directions in nutritional immunology as part of a symposium organized by the Canadian Nutrition Society. Objectives included (1) creating an understanding of the complex interplay between diet and the immune system from infants through to older adults, (2) illustrating the role of micronutrients that are vital to the immune system, (3) learning about current research comparing the impact of various dietary patterns and novel approaches to reduce inflammation, autoimmune conditions, allergies, and infections, and (4) discussing select dietary recommendations aimed at improving disease-specific immune function. The aims of this review are to summarize the symposium and to identify key areas of research that require additional exploration to better understand the dynamic relationship between nutrition and immune function.

The role of omega-3 polyunsaturated fatty acids in the intensive care unit.

PURPOSE OF REVIEW: This review provides an update on the actions of omega-3 polyunsaturated fatty acids (PUFAs) and presents the most recent findings from trials in patients in the intensive care unit (ICU) setting including relevant meta-analyses. Many specialized pro-resolving mediators (SPMs) are produced from bioactive omega-3 PUFAs and may explain many of the beneficial effects of omega-3 PUFAs, although other mechanisms of action of omega-3 PUFAs are being uncovered. RECENT FINDINGS: SPMs resolve inflammation, promote healing and support antiinfection activities of the immune system. Since publication of the ESPEN guidelines, numerous studies further support the use of omega-3 PUFAs. Recent meta-analyses favor the inclusion of omega-3 PUFAs in nutrition support of patients with acute respiratory distress syndrome or sepsis. Recent trials indicate that omega-3 PUFAs may protect against delirium and liver dysfunction in patients in the ICU, although effects on muscle loss are unclear and require further investigation. Critical illness may alter omega-3 PUFA turnover. There has been significant discussion about the potential for omega-3 PUFAs and SPMs in treatment of coronavirus disease 2019. SUMMARY: Evidence for benefits of omega-3 PUFAs in the ICU setting has strengthened through new trials and meta-analyses. Nevertheless, better quality trials are still needed. SPMs may explain many of the benefits of omega-3 PUFAs.

Foods to deliver immune-supporting nutrients.

PURPOSE OF REVIEW: This article will briefly describe the role of specific dietary components, mainly micronutrients, in supporting the immune response and summarise the literature regarding foods and dietary patterns in the context of immunity and infectious illness. Literature on SARS-COV-2 infection and COVID-19 is referred to where appropriate. RECENT FINDINGS: Micronutrients, other nutrients and plant bioactives have roles in supporting the immune response. Low status of a number of micronutrients is associated with increased risk and severity of COVID-19. Recent studies report associations of plant-based diets with lower risk of, and less severe, COVID-19. SUMMARY: In order to support the immune response, sufficient amounts of a range of essential and non-essential nutrients and other bioactives, mainly from a plant-based diet should be consumed. Further research should define cause-and-effect relationships of intakes of individual dietary components and foods, and of dietary patterns with susceptibility to, and severity of, viral infections.

Body mass index and clinical outcome of severe COVID-19 patients with acute hypoxic respiratory failure: Unravelling the "obesity paradox" phenomenon.

BACKGROUND AND AIMS: Although obesity have been generally shown to be an independent risk factor for poor outcomes in COVID-19 infection, some studies demonstrate a paradoxical protective effect ("obesity paradox"). This study examines the influence of obesity categories on clinical outcomes of severe COVID-19 patients admitted to an intensive care unit with acute hypoxic respiratory failure requiring either non-invasive or invasive mechanical ventilation. METHODS: This is a single centre, retrospective study of consecutive COVID-19 patients admitted to the intensive care unit between 03/2020 to 03/2021. Patients were grouped according to the NICE Body Mass Index (BMI) category. Admission variables including age, sex, comorbidities, and ICU severity indices (APACHE-II, SOFA and PaO2/FiO2) were collected. Data were compared between BMI groups for outcomes such as need for invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and 28-day and overall hospital mortality. RESULTS: 340 patients were identified and of those 333 patients had their BMI documented. Just over half of patients (53%) had obesity. Those with extreme obesity (obesity groups II and III) were younger with fewer comorbidities, but were more hypoxaemic at presentation, than the healthy BMI group. Although non-significant, obesity groups II and III paradoxically showed a lower in-hospital mortality than the healthy weight group. However, adjusted (age, sex, APACHE-II and CCI) competing risk regression analysis showed three-times higher mortality in obese category I (sub-distribution hazard ratio = 3.32 (95% CI 1.30-8.46), p = 0.01) and a trend to higher mortality across all obesity groups compared to the healthy weight group. CONCLUSIONS: In this cohort, those with obesity were at higher risk of mortality after adjustment for confounders. We did not identify an "obesity paradox" in this cohort. The obesity paradox may be explained by confounding factors such as younger age, fewer comorbidities, and less severe organ failures. The impact of obesity on indicators of morbidity including likelihood of requirement for organ support measures was not conclusively demonstrated and requires further scrutiny.

Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults-A Narrative Review and Call for Action.

The immune system is weakened by advancing age, often referred to as immunosenescence, increasing the vulnerability to, and frequently the severity of, infectious diseases in older people. This has become very apparent in the current coronavirus disease 2019 (COVID-19) pandemic for which older people are at higher risk of severe outcomes, even those who are fully vaccinated. Aging affects both the innate and adaptive immune systems and is characterized by an imbalanced inflammatory response. Increasing evidence shows that optimal status of nutrients such as vitamins C, D, and E and selenium and zinc as well as the omega-3 (n-3) fatty acids DHA and EPA can help compensate for these age-related changes. While inadequate intakes of these nutrients are widespread in the general population, this is often more pronounced in older people. Maintaining adequate intakes is a challenge for them due to a range of factors such as physical, physiological, and cognitive changes; altered absorption; and the presence of noncommunicable diseases. While nutritional requirements are ideally covered by a balanced diet, this can be difficult to achieve, particularly for older people. Fortified foods and nutritional complements are effective in achieving adequate micronutrient intakes and should be considered as a safe and cost-effective means for older people to improve their nutritional status and hence support their defense against infections. Complementing the diet with a combination of micronutrients, particularly those playing a key role in the immune system such as vitamins C, D, and E and selenium and zinc as well as DHA and EPA, is recommended for older people. Optimal nutrition to support the immune system in older people will remain essential, particularly in the face of the current COVID-19 pandemic and, thus, developing strategies to ensure adequate nutrition for the growing number of older adults will be an important and cost-effective investment in the future.

Micronutrients to Support Vaccine Immunogenicity and Efficacy.

The world has entered the third year of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is the primary public health strategy to protect against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in addition to other measures, such as mask wearing and social distancing. Vaccination has reduced COVID-19 severity and mortality dramatically. Nevertheless, incidence globally remains high, and certain populations are still at risk for severe outcomes. Additional strategies to support immunity, including potentially enhancing the response to vaccination, are needed. Many vitamins and trace minerals have recognized immunomodulatory actions, and their status and/or supplementation have been reported to correspond to the incidence and severity of infection. Furthermore, a variety of observational and some interventional studies report that adequate micronutrient status or micronutrient supplementation is associated with enhanced vaccine responses, including to COVID-19 vaccination. Such data suggest that micronutrient supplementation may hold the potential to improve vaccine immunogenicity and effectiveness, although additional interventional studies to further strengthen the existing evidence are needed. Positive findings from such research could have important implications for global public health, since deficiencies in several micronutrients that support immune function are prevalent in numerous settings, and supplementation can be implemented safely and inexpensively.

Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial.

BACKGROUND: It is unclear to what extent adjuvant dietary intervention can influence inflammation in rheumatoid arthritis (RA). OBJECTIVES: The objective was to assess the effects of dietary manipulation on inflammation in patients with RA. METHODS: In a crossover design, participants [n = 50, 78% females, median BMI (in kg/m2) 27, median age 63 y] were randomly assigned to begin with either a 10-wk portfolio diet of proposed anti-inflammatory foods (i.e., a high intake of fatty fish, whole grains, fruits, nuts, and berries) or a control diet resembling a Western diet with a 4-mo washout in between. This report evaluates the secondary outcome markers of inflammation among participants with stable medication. Analyses were performed using a linear mixed ANCOVA model. RESULTS: There were no significant effects on CRP or ESR in the group as a whole. In those with high compliance (n = 29), changes in ESR within the intervention diet period differed significantly compared with changes within the control diet period (mean: -5.490; 95% CI: -10.310, -0.669; P = 0.027). During the intervention diet period, there were lowered serum concentrations of C-X-C motif ligand 1 (CXCL1) (mean: -0.268; 95% CI: -0.452, -0.084;P = 0.006), CXCL5 (mean: -0.278; 95% CI: -0.530, -0.026 P = 0.031), CXCL6 (mean: -0.251; 95% CI: -0.433, -0.069; P = 0.009), and tumor necrosis factor ligand superfamily member 14 (TNFSF14) (mean: -0.139; 95% CI: -0.275, -0.002; P = 0.047) compared with changes within the control diet period. CONCLUSION: A proposed anti-inflammatory diet likely reduced systemic inflammation, as indicated by a decreased ESR in those who completed the study with high compliance (n = 29). These findings warrant further studies to validate our results, and to evaluate the clinical relevance of changes in CXCL1, CXCL5, CXCL6, and TNFSF14 in patients with RA.

Nutrition and immunity: lessons for COVID-19.

The role of the immune system is to protect the individual against pathogenic organisms. Nutrition is one of multiple factors that determines the immune response and good nutrition is important in supporting the immune response. Immunity can be impaired in older people, particularly those who are frail, in those living with obesity, in those who are malnourished and in those with low intakes of micronutrients. The immune impairments associated with nutritional inadequacy increase susceptibility to infection and permit infections to become more severe, even fatal. The adverse impact of poor nutrition on the immune system, including its inflammatory component, may be one of the explanations for the higher risk of more severe outcomes from infection with SARS-CoV-2 seen in older people and in those living with obesity. Studies of individual micronutrients including vitamin D and zinc suggest roles in reducing severity of infection with SARS-CoV-2. Good nutrition is also important in promoting a diverse gut microbiota, which in turn supports the immune system. The importance of nutrition in supporting the immune response also applies to assuring robust responses to vaccination. There are many lessons from the study of nutrition and immunity that are relevant for the battle with SARS-CoV-2.

Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app.

OBJECTIVES: Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. DESIGN: App-based community survey. SETTING: 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). MAIN EXPOSURE: Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. MAIN OUTCOME MEASURES: SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. RESULTS: In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. CONCLUSION: In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021.

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose-response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.

Nutrition and immunity: lessons for COVID-19.

The role of the immune system is to protect the individual against pathogenic organisms. Nutrition is one of multiple factors that determines the immune response and good nutrition is important in supporting the immune response. Immunity can be impaired in older people, particularly those who are frail, in those living with obesity, in those who are malnourished and in those with low intakes of micronutrients. The immune impairments associated with nutritional inadequacy increase susceptibility to infection and permit infections to become more severe, even fatal. The adverse impact of poor nutrition on the immune system, including its inflammatory component, may be one of the explanations for the higher risk of more severe outcomes from infection with SARS-CoV-2 seen in older people and in those living with obesity. Studies of individual micronutrients including vitamin D and zinc suggest roles in reducing severity of infection with SARS-CoV-2. Good nutrition is also important in promoting a diverse gut microbiota, which in turn supports the immune system. The importance of nutrition in supporting the immune response also applies to assuring robust responses to vaccination. There are many lessons from the study of nutrition and immunity that are relevant for the battle with SARS-CoV-2.

Bronchiectasis-Could Immunonutrition Have a Role to Play in Future Management?

Bronchiectasis is a chronic condition in which areas of the bronchial tubes become permanently widened predisposing the lungs to infection. Bronchiectasis is an age-associated disease with the highest prevalence in people older than 75 years. While the prevalence of bronchiectasis is higher in males, disease is more severe in females who have a poorer prognosis. The overall prevalence of the disease is thought to be rising. Its aetiology is multi-faceted, but a compromised immune system is now thought to play a central role in the pathology of this disease. Research has begun to study the role of malnutrition and certain nutrients-vitamin D and zinc-along with the role of the lung microbiome in relation to the management of bronchiectasis. Given this, the present mini review sets out to provide an overview of the state-of-the-art within the field, identify research gaps and pave the way for future developments and research investment within this field.

Nutrition, immunity and COVID-19.

The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B6, B12, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.

Response to Bistrian BR. Parenteral Fish-Oil Emulsions in Critically Ill COVID-19 Emulsions.

In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish-oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID-19). We consider that immune-modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish-oil emulsions, may be important to change the course of COVID-19's death pathway. Prescriptions should be based on body weight (eg, 0.2-g pure fish-oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish-oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.