Nutrition and the Covid-19 pandemic: Three factors with high impact on community health.

AIMS: In the course of the COVID-19 pandemic, multiple suggestions have been delivered through websites and social media referring to natural substances and various kinds of supplements with thaumaturgical properties in preventing and/or fighting the coronavirus infection. Indeed, there is no clinical trial evidence that a dietary or pharmacological supplementation of any particular substance will increase the effectiveness of the immune defences. There are however three nutritional issues that deserve special attention under the present circumstances, namely vitamin D deficiency, excess salt intake and inappropriate alcohol consumption. Here is a short review of the current knowledge about the possible role of these factors in the immunity defence system and their potential impact on the modulation of the immune response to SARS-COV2 infection. DATA SYNTHESIS: For all of these factors there is convincing evidence of an impact on the immune defence structure and function. In the absence of RCT demonstration that increased ingestion of any given substance may confer protection against the new enemy, special attention to correction of these three nutritional criticisms is certainly warranted at the time of COVID pandemic. CONCLUSIONS: We propose that the inappropriate intake of salt and alcohol and the risk of inadequate vitamin D status should be object of screening, in particular in subjects at high mortality risk from SARS-COV 2 infection, such as institutionalised elderly subjects and all those affected by predisposing conditions.

Development, Prevention, and Treatment of Alcohol-Induced Organ Injury: The Role of Nutrition.

Alcohol and nutrition have the potential to interact at multiple levels. For example, heavy alcohol consumption can interfere with normal nutrition, resulting in overall malnutrition or in deficiencies of important micronutrients, such as zinc, by reducing their absorption or increasing their loss. Interactions between alcohol consumption and nutrition also can affect epigenetic regulation of gene expression by influencing multiple regulatory mechanisms, including methylation and acetylation of histone proteins and DNA. These effects may contribute to alcohol-related organ or tissue injury. The impact of alcohol-nutrition interactions has been assessed for several organs and tissues, including the intestine, where heavy alcohol use can increase intestinal permeability, and the liver, where the degree of malnutrition can be associated with the severity of liver injury and liver disease. Alcohol-nutrition interactions also play a role in alcohol-related lung injury, brain injury, and immune dysfunction. Therefore, treatment involving nutrient supplementation (e.g., with zinc or S-adenosylmethionine) may help prevent or attenuate some types of alcohol-induced organ damage.

Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers.

BACKGROUND: Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of this study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls. METHODS: Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress [S], relaxing [R], and alcohol cue [C]), followed by the "alcohol taste test" (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, 1 per day in a randomized and counterbalanced order. Measures of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), alcohol craving, and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT. RESULTS: Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress- and cue-induced alcohol craving and anxiety and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake, and severity of problem drinking. CONCLUSIONS: Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.

Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers.

N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers. This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine. No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine. In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins. Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. The clinical significance of these findings remains to be elucidated.

Immunoglobulin E sensitization to cross-reactive carbohydrate determinants: epidemiological study of clinical relevance and role of alcohol consumption.

BACKGROUND: The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal. OBJECTIVE: To investigate the relationship of alcohol consumption with CCD sensitization, the role of alcohol dehydrogenase gene polymorphisms, and the clinical consequences of CCD sensitization. METHODS: Serum-specific IgE sensitization (> or =0.1 kU/l) to a CCD (the N-glycan from bromelain) was assessed in 1,197 adults participating in a population-based study in Copenhagen, Denmark. Alcohol consumption and atopic symptoms (rhinitis, asthma and oral allergy syndrome) were assessed by questionnaire. Examinations included skin prick tests (SPTs), qualitative multiallergen IgE test (Phadiatop), methacholine bronchial hyperreactivity, eosinophil cationic protein and alcohol dehydrogenase (ADH) gene polymorphisms. RESULTS: Alcohol consumption was significantly associated with CCD sensitization and this was particularly evident in SPT-negative individuals. The fast-metabolizing allele of the ADH1b polymorphism was significantly associated with CCD sensitization in alcohol drinkers. CCD sensitization was associated with atopic symptoms, but associations attenuated markedly when adjusting for SPT reactivity. CONCLUSIONS: Our results suggest that the positive association between alcohol consumption and CCD sensitization is universal and not specific to certain populations. The observed association between the ADH1b polymorphism and CCD sensitization may support that alcohol is causally related to the risk of CCD sensitization. The observed association between CCD sensitization and atopic phenotypes did not appear to be independent of SPT reactivity indicating limited significance of CCD sensitization per se.

Immunoglobulin-E reactivity to a glycosylated food allergen (peanuts) due to interference with cross-reactive carbohydrate determinants in heavy drinkers.

BACKGROUND: N-glycans in plant and invertebrate glycoproteins can induce extensive IgE cross-reactivity therefore limiting the specificity of in vitro allergy tests. IgE sensitization to N-glycans (cross-reactive carbohydrate determinants, CCDs) may be increased in heavy drinkers, who therefore show IgE reactivity to aeroallergens, latex, and Hymenoptera venoms. The peanut, a CCD-bearing allergen, is the leading cause of severe food allergic reactions in many populations. AIM OF THE STUDY: To investigate the potential interference of CCDs with determinations of IgE to peanuts in heavy drinkers. METHODS: We determined IgE to peanuts and IgE to a CCD marker (MUXF(3), the N-glycan from bromelain) in 41 heavy drinkers admitted to the hospital and 54 healthy controls. None of the participants reported symptoms of peanut allergy. In cases with positive (>or=0.35 kU/l) IgE to peanuts, we performed inhibition assays with a neoglycoprotein consisting of MUXF(3) molecules coupled to bovine serum albumin (MUXF(3)-BSA) and a similar neoglycoprotein lacking xylose and fucose (MM-BSA). In the same cases, we screened for IgE to a panel of recombinant nonglycosylated peanut allergens. SDS-PAGE immunoblotting and inhibition assays were performed in selected cases. RESULTS: The prevalence of positive IgE to peanuts was 22 and 3.7% in heavy drinkers and healthy controls, respectively (p < 0.001). Peanut-IgE positivity was closely related to the presence of IgE to CCDs. In most (8/9) heavy drinkers with positive IgE to peanuts, reactivity was inhibited by preincubation with MUXF(3)-BSA, but not with MM-BSA. IgE binding to multiple bands on immunoblotting studies was also inhibited by MUXF(3)-BSA preincubation. IgE to nonglycosylated recombinant peanut allergens was uniformly negative. CONCLUSION: Heavy drinking is associated with clinically asymptomatic IgE reactivity to peanuts, a relevant food allergen, in relation to CCD interference.

Interference of cross-reactive carbohydrates in the determination of specific IgE in alcohol drinkers and strategies to minimize it: the example of latex.

BACKGROUND: Cross-reactive carbohydrate determinants (CCDs) are N-glycans in plant and invertebrate proteins that interfere with specific IgE determinations. The prevalence of IgE to Man2XylFucGlcNAc2 (MUXF), the CCD from bromelain, may be increased in heavy drinkers. OBJECTIVE: To further investigate the relationship of alcohol consumption to CCD specific IgE. Latex was used as an example for investigating CCD interference with in vitro allergy testing and how to minimize the interference by using nonglycosylated recombinant allergens and inhibition assays. METHODS: We determined the levels of IgE to CCD markers (MUXF and ascorbate oxidase) and natural rubber latex in 270 adults without a history of latex allergy (73 abstainers or occasional drinkers, 76 light drinkers, 47 moderate drinkers, and 74 heavy drinkers). In cases with latex reactivity, we performed inhibition assays with MUXF and screened for IgE to a panel of recombinant latex allergens. Fourteen-day serologic follow-up was available for a subset of individuals. RESULTS: Moderate to heavy drinkers displayed an increased prevalence of IgE to CCD markers. The presence of CCD specific IgE was closely associated with latex IgE reactivity. Inhibition studies and the absence of reactivity to nonglycosylated recombinant latex allergens indicated CCD interference in latex IgE determinations. Serum levels of specific IgE decreased with alcohol abstention. CONCLUSIONS: In this population, alcohol consumption is associated with an increased prevalence of IgE reactivity to natural rubber latex due to CCD interference. The use of nonglycosylated recombinant allergens and inhibition assays may help to minimize CCD interference in populations in which IgE to CCDs is common.

Sensitization to cross-reactive carbohydrate determinants in relation to alcohol consumption.

BACKGROUND: Alcohol consumption is associated with increased serum IgE of unknown specificity. OBJECTIVE: To investigate the prevalence of specific IgE to cross-reactive carbohydrate determinants (CCDs) in adults, and its relation to alcohol consumption. METHODS: Population-based survey of 457 adults (218 abstainers, 195 light-to-moderate drinkers, 44 heavy drinkers). Specific IgE determinations included a CCD (MUXF(3), the N-glycan of bromelain), pollens (Lolium perenne and Olea europaea), Hymenoptera venoms (Apis mellifera and Vespula spp.), and a mite (Dermatophagoides pteronyssinus). We replicated these studies in an additional sample of alcoholics (n=138). Inhibition assays were performed in selected cases. RESULTS: In the general population, 5.6% of individuals (95% confidence interval 3.5-7.6%) showed positive (>/=0.35 kU/L) CCD-specific IgE. The levels of CCD-specific IgE were particularly high in heavy drinkers, who also showed a high prevalence of positive IgE to pollens and Hymenoptera venoms, doubling (at least) the prevalence found in alcohol abstainers and light-to-moderate drinkers. The presence of IgE to pollens and Hymenoptera venoms was closely correlated with the presence of CCD-specific IgE. These features were confirmed in the additional sample of alcoholics. Inhibition studies indicated a role of CCD interference in IgE positivity to pollen and Hymenoptera allergens in alcoholics. CONCLUSIONS: CCD-specific IgE is prevalent in heavy drinkers, and is associated with positive IgE to pollens and Hymenoptera venoms. Specific IgE results should be interpreted with caution in heavy drinkers.

Influences of distress and alcohol consumption on the development of a delayed-type hypersensitivity skin test response.

OBJECTIVE: This paper reports the effects of naturally occurring levels of distress on the development of delayed-type hypersensitivity (DTH) skin test responses. These in vivo measures provide a biologically relevant assessment of cellular immune competence. METHODS: Subjects (N = 166) were immunized (baseline) with the novel antigen, keyhole limpet hemocyanin (KLH), and DTH skin test responses against KLH were assessed 3 weeks later (follow-up). The CMI Multitest (Merieux, France), which evaluates DTH responses to a panel of seven antigens, was also administered at follow-up. Emotional distress was assessed at baseline and follow-up by the Profile of Mood States. RESULTS: Distress levels at baseline were associated with a reduced likelihood of developing DTH responses against KLH at follow-up (r = -0.22, p =.01). There was no relationship between distress at follow-up and cutaneous DTH in response to KLH (r = 0.09, p =.24) or in the Multitest (r = -0.03, p =.70). In addition, higher levels of alcohol consumption at baseline (r = -0.19, p =.02) and at follow-up (r = -0.20, p =.01) were associated with a decreased likelihood of developing cutaneous DTH against KLH. CONCLUSIONS: Everyday levels of distress predicted the capacity of the cellular arm of the immune system to exhibit recall responses to an antigen, when the experimental paradigm allowed the assessment of distress at the time of antigen sensitization. Moderate alcohol consumption independently affected cutaneous DTH.

Immune dysfunction during alcohol consumption and murine AIDS: the protective role of dehydroepiandrosterone sulfate.

Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by the human immunodeficiency virus (HIV) after development of severe immunosuppressive changes. Chronic ethanol (EtOH) consumption accentuates the severity of murine AIDS (MAIDS). Because hormone production is often suppressed by chronic EtOH intake, as well as retrovirus infection, we investigated whether hormone supplementation during chronic EtOH consumption contributes to slowing immune dysfunction caused by LP-BM5 infection and/or EtOH use. Because dehydroepiandrosterone sulfate (DHEAS) was previously shown to have immune-enhancing properties during MAIDS, we determined whether DHEAS reduced cytokine dysregulation otherwise exacerbated by chronic EtOH intake during MAIDS. Adult female C57BL/6 mice were infected with LP-BM5 murine retrovirus. Some were fed 40% EtOH in drinking water and agar gel for 16 weeks postinfection. EtOH consumption further inhibited T- and B-cell proliferation beyond suppression due to retrovirus infection. Interleukin (IL)-2 release produced by concanavalin A-stimulated splenocytes was reduced by EtOH use by infected and uninfected mice. DHEAS overcame much of the effects induced by retrovirus infection and/or EtOH use. IL-4 secretion and IL-6 secretion were enhanced. Hepatic vitamin E levels were decreased by murine retrovirus infection, as well as by EtOH use in both uninfected and infected mice. In addition, DHEAS (0.01%) supplementation during MAIDS prevented the further dysregulation of cytokines and hepatic lipid peroxidation due to EtOH intake, partially restored T- and B-cell proliferation, and maintained hepatic vitamin E levels to near normal levels.

The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy.

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.

The association of alcohol consumption with self-reported illness in university students.

Many reports over the years have indicated an association between alcohol consumption and infectious illness among chronic heavy drinkers; however, many patients in these studies have been chronically ill. Thus the question of whether alcohol can appreciably influence immunity in humans and affect the incidence of infectious diseases remains largely unanswered. For this study over 1,100 undergraduate students from a general education course at a large midwestern university were surveyed. Students were asked about their drinking habits and acute health problems. Analyses of their self-reports showed no increase in acute health problems or upper respiratory infections in students drinking between one and 21 drinks per week. However, students drinking 28 or more alcoholic drinks per week had significantly more health problems in the aggregate and those drinking more than 22 drinks per week had more upper respiratory infections than other students including nondrinkers. It was concluded that excessive alcohol intake increased the risk of respiratory infections and acute illnesses in these students, but more moderate alcohol consumption had little effect on the risk for these health problems.

Resistance to intestinal parasites during murine AIDS: role of alcohol and nutrition in immune dysfunction.

A murine AIDS model with many similarities to human AIDS, LP-BM5 Murine Leukaemia, suppresses T and B cell numbers and functions in the intestine. This permits chronic colonization by Giardia and Cryptosporidium. Cocaine and the nutrient alcohol, which are immunosuppressive, further reduce resistance to intestinal parasites and intestinal lymphocyte numbers. Protein undernutrition, vitamin E supplementation, and alcohol use further modify immune dysfunction induced by the murine retrovirus infection. This suggests that both undernutrition and nutrient supplementation could affect parasite resistance during AIDS. Thus this murine model of human AIDS has great potential to accelerate studies of the role of nutrients in immune dysfunction and resistance to intestinal parasites.