IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Red Meat Intake and the Risk of Cardiovascular Diseases: A Prospective Cohort Study in the Million Veteran Program.

BACKGROUND: Red meat consumption was associated with an increased risk of cardiovascular disease (CVD) in prospective cohort studies and a profile of biomarkers favoring high CVD risk in short-term controlled trials. However, several recent systematic reviews and meta-analyses concluded with no or weak evidence for limiting red meat intake. OBJECTIVES: To prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds. METHODS: Our study included 148,506 participants [17,804 female (12.0%)] who were free of cancer, diabetes, and CVD at baseline from the Million Veteran Program. A food frequency questionnaire measured red meat intakes at baseline. Nonfatal myocardial infarction and acute ischemic stroke were identified through a high-throughput phenotyping algorithm, and fatal CVD events were identified by searching the National Death Index. RESULTS: Comparing the extreme categories of intake, the multivariate-adjusted relative risks of CVD was 1.18 (95% CI: 1.01, 1.38; P-trend < 0.0001) for total red meat, 1.14 (95% CI: 0.96, 1.36; P-trend = 0.01) for unprocessed red meat, and 1.29 (95% CI: 1.04, 1.60; P-trend = 0.003) for processed red meat. We observed a more pronounced positive association between red meat intake and CVD in African American participants than in White participants (P-interaction = 0.01). Replacing 0.5 servings/d of red meat with 0.5 servings/d of nuts, whole grains, and skimmed milk was associated with 14% (RR: 0.86; 95% CI: 0.83, 0.90), 7% (RR: 0.93; 95% CI: 0.89, 0.96), and 4% (RR: 0.96; 95% CI: 0.94, 0.99) lower risks of CVD, respectively. CONCLUSIONS: Red meat consumption is associated with an increased risk of CVD. Our findings support lowering red meat intake and replacing red meat with plant-based protein sources or low-fat dairy foods as a key dietary recommendation for the prevention of CVD.

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk.

BACKGROUND: Considerable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. OBJECTIVE: The purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. METHODS: Secondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. RESULTS: Of the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = -0.494; P = 0.086) and insulin concentrations (r = -0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = -0.642; P = 0.024) and ß cell function (r = -0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. CONCLUSIONS: These data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight. This study was registered at clinicaltrials.gov as NCT02614729.

Age-Period-Cohort Analysis of Long-Term Trends in Ischemic Stroke Mortality in China Caused by Specific Risk Factors from 1990 to 2019.

OBJECTIVE: The objective of this study was to study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed joinpoint regression software and the age-period-cohort method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body mass index in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.

Red meat intake, faecal microbiome, serum trimethylamine N-oxide and hepatic steatosis among Chinese adults.

BACKGROUND AND AIMS: Emerging evidence suggests a detrimental impact of high red meat intake on hepatic steatosis. We investigated the potential interplay between red meat intake and gut microbiome on circulating levels of trimethylamine N-oxide (TMAO) and hepatic steatosis risk. METHODS: This cross-sectional study was conducted in a representative sample of 754 community-dwelling adults in Huoshan, China. Diet was collected using 4 quarterly 3 consecutive 24-h dietary (12-day) recalls. We profiled faecal microbiome using 16S ribosomal RNA sequencing and quantified serum TMAO and its precursors using LC-tandem MS (n = 333). We detected hepatic steatosis by FibroScan. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: TMAO levels but not its precursors were positively associated with the likelihood of hepatic steatosis (aOR per 1-SD increment 1.86, 95% CI 1.04-3.32). We identified 14 bacterial genera whose abundance was associated with TMAO concentration (pFDR < .05) belonging to the phyla Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria families. Per 10 g/day increase in red meat intake was positively associated with TMAO levels among participants who had higher red meat intake (>70 g/day) and higher TMAO-predicting microbial scores (TMS, ß = .045, p = .034), but not among others (pinteraction = .030). TMS significantly modified the positive association between red meat and steatosis (pinteraction = .032), with a stronger association being observed among participants with higher TMS (aOR 1.30, 95% CI 1.07-1.57). CONCLUSIONS: The bacterial genera that predicted TMAO levels may jointly modify the association between red meat intake and TMAO levels and the subsequent risk of hepatic steatosis.

Effects of red meat taxes and warning labels on food groups selected in a randomized controlled trial.

BACKGROUND: High consumption of red and processed meat contributes to both health and environmental harms. Warning labels and taxes for red meat reduce selection of red meat overall, but little is known about how these potential policies affect purchases of subcategories of red meat (e.g., processed versus unprocessed) or of non-red-meat foods (e.g., cheese, pulses) relevant to health and environmental outcomes. This study examined consumer responses to warning labels and taxes for red meat in a randomized controlled trial. METHODS: In October 2021, we recruited 3,518 US adults to complete a shopping task in a naturalistic online grocery store. Participants were randomly assigned to one of four arms: control (no warning labels or tax), warning labels only (health and environmental warning labels appeared next to products containing red meat), tax only (prices of products containing red meat were increased 30%) or combined warning labels + tax. Participants selected items to hypothetically purchase, which we categorized into food groups based on the presence of animal- and plant-source ingredients (e.g., beef, eggs, pulses), meat processing level (e.g., processed pork versus unprocessed pork), and meat species (e.g., beef versus pork). We assessed the effects of the warning labels and tax on selections from each food group. RESULTS: Compared to control, all three interventions led participants to select fewer items with processed meat (driven by reductions in processed pork) and (for the tax and warning labels + tax interventions only) fewer items with unprocessed meat (driven by reductions in unprocessed beef). All three interventions also led participants to select more items containing cheese, while only the combined warning labels + tax intervention led participants to select more items containing processed poultry. Except for an increase in selection of pulses in the tax arm, the interventions did not affect selections of fish or seafood (processed or unprocessed), eggs, or plant-based items (pulses, nuts & seeds, tofu, meat mimics, grains & potatoes, vegetables). CONCLUSIONS: Policies to reduce red meat consumption are also likely to affect consumption of other types of foods that are relevant to both health and environmental outcomes. TRIAL REGISTRATION: NCT04716010 on www. CLINICALTRIALS: gov .

Exploring the differences in serum metabolite profiles after intake of red meat in women with rheumatoid arthritis and a matched control group.

PURPOSE: Studies have suggested that women with RA tend to avoid red meat more often than women without RA, based on their perception that it exacerbates their symptoms. Therefore, the aim of this study is to investigate and compare the postprandial metabolic response following the consumption of a red meat meal in patients with RA and a matched control group. METHODS: Participants were challenged with a meal with red meat and blood samples were collected before and at 0.5, 1, 2, 3 and 5 h after the meal. Serum metabolites were quantified by Nuclear Magnetic Resonance (NMR) analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) was used to evaluate separation by metabolites due to diagnosis of RA or not and to identify changes in metabolites related to RA. Incremental area under the curve was calculated for univariate comparisons for 23 metabolites. RESULTS: The matched groups, including 22 women with RA and 22 women without RA, did not differ significantly in age, body mass index, diet quality or reported physical activity. OPLS-DA models had a limited quality indicating that there were no differences in metabolite patterns between the groups. However, phenylalanine was significantly higher in concentration in women with RA compared to controls in both fasting and postprandial samples. CONCLUSION: To conclude, this well-controlled postprandial intervention study found a significantly higher concentration of phenylalanine in both fasting and postprandial samples of women with RA compared to matched women without RA. These findings warrant further investigation in larger studies. TRIAL REGISTRATION: The PIRA (Postprandial Inflammation in Rheumatoid Arthritis) trial is Registered at Clinicaltrials.gov (NCT04247009).

A randomized controlled cross-over trial investigating the acute inflammatory and metabolic response after meals based on red meat, fatty fish, or soy protein: the postprandial inflammation in rheumatoid arthritis (PIRA) trial.

PURPOSE: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. METHODS: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. RESULTS: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. CONCLUSION: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.

Consumption of different types of meat and the risk of chronic limb-threatening ischemia: the Singapore Chinese Health Study.

BACKGROUND: Although red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI). METHODS: In a prospective study of 63,257 Chinese in Singapore, who were aged 45-74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease. Multivariable Cox models were used to examine associations between quartiles of meat intake and CLTI risk. RESULTS: After a mean follow-up of 18.8 years, there were 1069 cases of CLTI. Higher intake of red meat intake was associated with increased risk of CLTI in a stepwise manner. Comparing extreme quartiles of red meat intake, the hazard ratio (HR) for the association with CLTI risk was 1.24 [95% confidence interval (CI) = 1.03-1.49; P-trend = 0.02]. In stratified analysis, red meat intake had a stronger association with CLTI risk among those without diabetes [HR (95% CI) comparing extreme quartiles = 1.41 (1.10-1.80); P-trend = 0.03] than among those with diabetes at baseline [HR (95% CI) comparing extreme quartiles = 1.04 (0.79-1.38); P-trend = 0.05] (P-interaction = 0.03). Otherwise, the associations were not different by sex, BMI, smoking status, hypertension, alcohol consumption, or history of cardiovascular diseases. Using a theoretical model in substitution analysis that substituted three servings per week of red meat with poultry or fish/shellfish, the relative risk of CLTI was reduced by 13-14%. CONCLUSIONS: Consumption of red meat was associated with higher CLTI risk in this Asian cohort. Substituting red meat with poultry or fish/shellfish may reduce this risk.

Dietary pattern and precocious puberty risk in Chinese girls: a case-control study.

BACKGROUND: The role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chinese girls. METHODS: In this case-control study, we enrolled 185 precocious puberty girls and 185 age-matched controls. Their dietary intake was assessed through a semi-quantitative food frequency questionnaire. Their sociodemographic and lifestyle data were collected. The associations between dietary intake and risk of precocious puberty were assessed by conditional logistic regression models. RESULTS: After multivariate adjustment, consuming a higher amount of red meat was associated with higher precocious puberty risk (OR = 2.74, 95% CI: 1.25-6.02), while a higher frequency of fruit ( P for trend = 0.024) and amount of vegetable intake was associated with a lower risk of precocious puberty (P for trend = 0.002). The high vegetable and protein dietary pattern was significantly negatively associated with precocious puberty (OR = 0.78, 95% CI: 0.63-0.97), whereas the high animal food and fruits dietary pattern was remarkably positively associated with precocious puberty (OR = 1.36, 95% CI: 1.09-1.69), after adjusting for age and body mass index. CONCLUSIONS: High vegetable and protein dietary pattern is a protective factor against precocious puberty, while high animal food and fruits dietary pattern is a risk factor for precocious puberty in Chinese girls. Attentions should be paid to a reasonable intake of red meat, eggs, and fruits in children's daily diet, increase their intake of vegetables, in order to reduce the risk of precocious puberty.

Alpha-Gal, epitope responsible for allergy to red meat, in the Mediterranean tick Hyalomma lusitanicum.

Alpha-Gal/α-Gal is an oligosaccharide produced by non-primate mammals. Humans have developed an immune response mediated by anti-α-Gal antibodies that can trigger an allergic reaction and cause anaphylaxis. In recent years, cases of patients with delayed allergic reaction to mammalian meat have been reported worldwide. In Spain, these cases have been related to the species Ixodes ricinus L. (Ixodida: Ixodidae), whose distribution is located in the north of the country. In this work, the presence of α-Gal in water-soluble extracts from samples of salivary glands and digestive tracts of Hyalomma lusitanicum Koch (Ixodida: Ixodidae) both engorged and collected from vegetation were studied. The presence of that epitope was confirmed by the presence of reactive proteins of >250 kDa in both samples. The highest concentrations of α-Gal were detected in salivary glands. Neither sex nor diet influenced the concentration of α-Gal, which seems to indicate its endogenous production and its possible inoculation to the host during tick feeding.

The association between consumption of red and processed meats with metabolic syndrome and its components in obese and overweight women: a cross-sectional study.

OBJECTIVES: Previous studies have shown a relation between the consumption of different types of meats and chronic disorders. This study aims to investigate the association between red and processed meat intake with metabolic syndrome (MetS) and its components in healthy obese and overweight women. METHODS: This cross-sectional study was conducted on Iranian women. The dietary assessment and body composition were measured by a validated food frequency questionnaire (FFQ) and bioelectrical impedance analysis, respectively. Blood samples were collected by standard protocols. RESULTS: A total of 231 women (mean age 36.47 ± 8.44 years) were included in the current study. After controlling for potential confounders, there was a marginally significant associations between higher intake of processed meat with the MetS (OR:1.01, 95% CI: 0.94,2.94, P:0.06) and high serum triglycerides (TG) (OR:1.27, 95% CI: 0.94,2.98, P:0.07). There was a significant associations between high intake of red meats with lower odds of higher waist circumference (WC) (OR:0.31, 95% CI: 0.10,0.97, P:0.04). Also, there was a significant associations were found between high intake of processed meats with greater odds of having lower high-density lipoprotein cholesterol (HDL-c) (OR:0.64, 95% CI: 0.30,0.95, P:0.03). CONCLUSIONS: The current study suggests that higher intakes of processed meat may be associated with the MetS in Iranian women with excess body weight, while this was not the case for red meat. More studies however are necessary in different communities to draw definitive conclusions.

Adults' Beliefs Related to Reducing Red Meat Consumption: An exploratory study in the province of Quebec, Canada.

A significant consumption of red meat is associated with various issues (e.g. public health, sustainability, animal welfare). This exploratory study aims to identify the perceived advantages and disadvantages, perceived approval and disapproval by important others, and perceived barriers and facilitators pertaining to reducing red meat consumption among adults. An online questionnaire based on the Theory of Planned Behaviour was used to elicit the salient beliefs of 55 red meat eaters living in the province of Quebec (Canada). A content analysis performed by two independent coders revealed that the predominant themes (modal beliefs) included health, environment, saving money, food preferences, social influence, perceptions of the alternatives of meat, and efforts related to change. This study can inform the development of interventions aimed at promoting the reduction of red meat consumption.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children.

OBJECTIVE: Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. METHODS: Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. RESULTS: One hundred and twenty-seven (26%) children experienced CKD progression during 5 years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n = 1, dairy: n = 7, red and processed meat: n = 2, nuts and beans: n = 1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. CONCLUSIONS: Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Trimethylamine N-oxide is associated with long-term mortality risk: the multi-ethnic study of atherosclerosis.

AIMS: Little is known about associations of trimethylamine N-oxide (TMAO), a novel gut microbiota-generated metabolite of dietary phosphatidylcholine and carnitine, and its changes over time with all-cause and cause-specific mortality in the general population or in different race/ethnicity groups. The study aimed to investigate associations of serially measured plasma TMAO levels and changes in TMAO over time with all-cause and cause-specific mortality in a multi-ethnic community-based cohort. METHODS AND RESULTS: The study included 6,785 adults from the Multi-Ethnic Study of Atherosclerosis. TMAO was measured at baseline and year 5 using mass spectrometry. Primary outcomes were adjudicated all-cause mortality and cardiovascular disease (CVD) mortality. Secondary outcomes were deaths due to kidney failure, cancer, or dementia obtained from death certificates. Cox proportional hazards models with time-varying TMAO and covariates assessed the associations with adjustment for sociodemographics, lifestyles, diet, metabolic factors, and comorbidities. During a median follow-up of 16.9 years, 1704 participants died and 411 from CVD. Higher TMAO levels associated with higher risk of all-cause mortality [hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.08-1.17], CVD mortality (HR: 1.09, 95% CI: 1.00-1.09), and death due to kidney failure (HR: 1.44, 95% CI: 1.25-1.66) per inter-quintile range, but not deaths due to cancer or dementia. Annualized changes in TMAO levels associated with higher risk of all-cause mortality (HR: 1.10, 95% CI: 1.05-1.14) and death due to kidney failure (HR: 1.54, 95% CI: 1.26-1.89) but not other deaths. CONCLUSION: Plasma TMAO levels were positively associated with mortality, especially deaths due to cardiovascular and renal disease, in a multi-ethnic US cohort.

Red meat consumption, cardiovascular diseases, and diabetes: a systematic review and meta-analysis.

AIMS: Observational studies show inconsistent associations of red meat consumption with cardiovascular disease (CVD) and diabetes. Moreover, red meat consumption varies by sex and setting, however, whether the associations vary by sex and setting remains unclear. METHODS AND RESULTS: This systematic review and meta-analysis was conducted to summarize the evidence concerning the associations of unprocessed and processed red meat consumption with CVD and its subtypes [coronary heart disease (CHD), stroke, and heart failure], type two diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) and to assess differences by sex and setting (western vs. eastern, categorized based on dietary pattern and geographic region). Two researchers independently screened studies from PubMed, Web of Science, Embase, and the Cochrane Library for observational studies and randomized controlled trials (RCTs) published by 30 June 2022. Forty-three observational studies (N = 4 462 810, 61.7% women) for CVD and 27 observational studies (N = 1 760 774, 64.4% women) for diabetes were included. Red meat consumption was positively associated with CVD [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.05 to 1.16 for unprocessed red meat (per 100 g/day increment); 1.26, 95% CI 1.18 to 1.35 for processed red meat (per 50 g/day increment)], CVD subtypes, T2DM, and GDM. The associations with stroke and T2DM were higher in western settings, with no difference by sex. CONCLUSION: Unprocessed and processed red meat consumption are both associated with higher risk of CVD, CVD subtypes, and diabetes, with a stronger association in western settings but no sex difference. Better understanding of the mechanisms is needed to facilitate improving cardiometabolic and planetary health.

Characterization of an Aptamer Targeting Neu5Gc, as an Endogenous Pathogenic Factor Derived from Red Meat.

N-glycolylneuraminic acid (Neu5Gc), a sialic acid predominantly found in the non-neurohumoral fluids of hind-mouthed animals, is incapable of synthesizing Neu5Gc due to a deletion in the CMAH exon of the gene encoding human CMP-Neu5Gc hydroxylase. But consumption of animal-derived foods that contain Neu5Gc, such as red meat, can instigate an immune response in humans, as Neu5Gc is recognized as a foreign substance by the human immune system. This recognition leads to the production of anti-Neu5Gc antibodies, subsequently resulting in chronic inflammation. When Neu5Gc is consumed excessively or frequently, it may contribute to the development of heart disease and cancer. This makes Neu5Gc, an endogenous pathogenic factor derived from red meat, a new hot topic in red meat safety research. In this study, aptamers obtained by the magnetic bead SELEX technique were subjected to homology and secondary structure prediction analysis as well as affinity determination. The result indicated that the aptamer 2B.N2A9 exhibited a robust binding affinity, with an affinity constant (Ka) of 1.87 × 108 L/mol. This aptamer demonstrated optimal binding specificity within a pH range of 5.4 to 7.4. Molecular docking analysis further revealed that aptamer 2B.N2A9 formed stable binding interactions with the target Neu5Gc at specific sites, namely G-14, C-15, G-13, G-58, G-60, and C-59. An Enzyme-Linked Oligonucleotide Sorbent Assay (ELOSA) methodology was established to detect the endogenous pathogenic factor Neu5Gc present in red meat. This method demonstrated a limit of detection (LOD) of 0.71 ng/mL, along with an average recovery rate of 92.23%. The aptamer obtained in this study exhibited favorable binding properties to Neu5Gc. The assay was relatively convenient and demonstrated good sensitivity. Further investigation into the distribution of Neu5Gc in various red meats is of public health significance and scientific potential. A practical detection method should be provided to guide red meat diets and ensure the nutrition and safety of meat products.

N-glycolylneuraminic acid in red meat and processed meat is a health concern: A review on the formation, health risk, and reduction.

One of the most consistent epidemiological associations between diet and human disease risk is the impact of consuming red meat and processed meat products. In recent years, the health concerns surrounding red meat and processed meat have gained worldwide attention. The fact that humans have lost the ability to synthesize N-glycolylneuraminic acid (Neu5Gc) makes red meat and processed meat products the most important source of exogenous Neu5Gc for humans. As our research of Neu5Gc has increased, it has been discovered that Neu5Gc in red meat and processed meat is a key factor in many major diseases. Given the objective evidence of the harmful risk caused by Neu5Gc in red meat and processed meat to human health, there is a need for heightened attention in the field of food. This updated review has several Neu5Gc aspects given including biosynthetic pathway of Neu5Gc and its accumulation in the human body, the distribution of Neu5Gc in food, the methods for detecting Neu5Gc, and most importantly, a systematic review of the existing methods for reducing the content of Neu5Gc in red meat and processed meat. It also provides some insights into the current status and future directions in this area.

[TWO CASES OF α-GAL SYNDROME CAUSED BY INGESTION OF WILD BOAR MEAT].

α-Gal syndrome (AGS) is an allergic reaction to galactose-α-1,3-galactose (α-gal) found in the salivary glands of ticks, mammalian meat excluding primates, and some antibody preparations, such as cetuximab. We report two cases of AGS diagnosed after ingestion of wild boar meat. Patient 1, a male in his 70s, developed anaphylactic shock about 3 h after eating wild boar meat. He was transported to our acute and critical care center in Nagasaki University Hospital because he had difficulty in moving. Patient 2, a female in her 60s, developed a skin rash about 2.5 h after ingesting wild boar meat. After visiting our department to investigate the cause of the disease, the sera of both patients were found to be positive for α-gal specific IgE antibody and were diagnosed with AGS caused by ingestion of wild boar meat. Reports of AGS diagnosed after ingestion of wild boar meat are rare in Japan. Compared with other prefectures, the consumption of wild boar meat in Nagasaki is relatively high in Japan. In the past 10 years, four cases of AGS were diagnosed at our department, half of which were caused by the ingestion of wild boar meat, the ratio is possibly higher than that in other prefectures in Japan.