Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial.

BACKGROUND: Inflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of coronavirus disease 2019 (COVID-19) infections. OBJECTIVES: This study aimed to examine the effects of a novel food supplement, palmitoylethanolamide (PEA), specifically Levagen+, as compared with a placebo on proinflammatory biomarkers in adults recently diagnosed with COVID-19 who were unvaccinated and nonhospitalized. METHODS: This study was a double-blind randomized placebo-controlled trial conducted October 2020-March 2021 (clinicaltrials.gov: NCT04912921). Participants aged 19-53 y were unvaccinated and recently infected with COVID-19 as indicated by a positive test result per RT-PCR or antigen test, and they reported to the test site following diagnosis as allowed by the CDC's return-to-work policy. Participants were stratified by age, sex, and BMI and randomly assigned by coin toss to receive 600 mg Levagen+ twice daily (LEV) or placebo tablets twice daily (CON) for 4 wk. At baseline and week 4, participants completed health histories, 24-h dietary recalls, anthropometrics, and nonfasting blood sampling. The primary outcomes were the 4-wk change between groups for IL-6, C-reactive protein, ferritin, intercellular adhesion molecule 1, soluble P-selectin (sP-selectin), and neutrophil/lymphocyte ratio. Multiple linear regression models were utilized to assess treatment effects on outcomes, adjusting for covariates. RESULTS: A total of 60 participants completed the study (LEV: n = 30; CON: n = 30). After 4 wk of supplementation, sP-selectin (ß = -11.5; 95% CI: -19.8, -3.15; P = 0.0078), IL-1ß (ß = -22.9; 95% CI: -42.4, -3.40; P = 0.0222), and IL-2 (ß = -1.73; 95% CI: -3.45, -0.065; P = 0.0492) concentrations were significantly reduced in the LEV group compared with the CON group. CONCLUSIONS: Inflammatory mechanisms are crucial to optimal resolution of infectious conditions, yet unchecked secretion of inflammatory mediators can promote the dysregulated immune response implicated in COVID-19 complications. Overall, PEA supplementation produced anti-inflammatory effects in individuals recently diagnosed with COVID-19 who were nonhospitalized.

Body Mass Index Is Associated with Post-Acute Elevations in Biomarkers of Platelet Activation and Inflammation in Unvaccinated Adults Diagnosed with COVID-19 in the Previous 8 Weeks.

INTRODUCTION: Obesity has arisen as a prominent risk factor for COVID-19 severity and long COVID, potentially owed in part to the obesity-induced proinflammatory state. This study aimed to examine relationships among circulating inflammatory biomarkers and body mass index in nonhospitalized adults recently diagnosed with COVID-19. METHODS: This analysis included participants who completed a randomized placebo-controlled trial conducted in October 2020-March 2021. Participants (19-53 years) were unvaccinated and enrolled following COVID-19 diagnosis as allowed by CDC return-to-work guidance. Anthropometrics and biomarkers were assessed at study baseline and week four. We examined the associations between body mass index (BMI) and inflammatory biomarkers via multiple regression models. RESULTS: At study baseline (i.e., the point of enrollment following COVID-19 diagnosis) across all participants (N = 60), a higher BMI was associated with elevations in several inflammatory biomarkers including IL-6 (ß = 7.63, 95% CI = 3.54, 11.89, p = 0.0004), ferritin (ß = 6.31, 95% CI = 1.97, 10.83, p = 0.0047), high sensitivity C-reactive protein (ß = 13.1, 95% CI = 8.03, 18.42, p = < 0.0001), tumor necrosis factor-α (ß = 3.23, 95% CI = 0.91, 5.60, p = 0.0069), IL-12p40 (ß = 3.69, 95% CI = 0.93, 6.52, p = 0.0094), IL-13 (ß = 5.11, 95% CI = 1.00, 9.40, p = 0.0154), and IL-1Ra (ß = 7.57, 95% CI = 3.61, 11.70, p = 0.0003). In control group participants (n = 30) after 4 weeks, a higher BMI was associated with elevations in IL-4 (ß = 17.8, 95% CI = 0.84, 37.6, p = 0.0397) and sP-selectin (ß = 1.16, 95% CI = 0.22, 2.11, p = 0.0182), controlling for baseline and covariates. CONCLUSIONS: Here, BMI was positively associated with circulating biomarkers of platelet activation and inflammation in adults recently diagnosed with COVID-19 after 4 weeks. The shift in post-acute COVID-19 inflammatory biomarkers associated with an increasing BMI noted here shares similarities to biomarkers of LC reported in the literature.

Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial.

Depressive disorders are the most prevalent mental health conditions in the world. The commonly prescribed antidepressant medications can have serious side effects, and their efficacy varies widely. Thus, simple, effective adjunct therapies are needed. Vinegar, a fermented acetic acid solution, is emerging as a healthful dietary supplement linked to favorable outcomes for blood glucose management, heart disease risk, and adiposity reduction, and a recent report suggests vinegar may improve symptoms of depression. This randomized controlled study examined the 4-week change in scores for the Center for Epidemiological Studies Depression (CES-D) questionnaire and the Patient Health Questionnaire (PHQ-9) in healthy overweight adults ingesting 2.95 g acetic acid (4 tablespoons vinegar) vs. 0.025 g acetic acid (one vinegar pill) daily. A secondary objective explored possible underlying mechanisms using metabolomics analyses. At week 4, mean CES-D scores fell 26% and 5% for VIN and CON participants respectively, a non-significant difference between groups, and mean PHQ-9 scores fell 42% and 18% for VIN and CON participants (p = 0.036). Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN participants compared to controls, metabolic alterations previously linked to improved mood. Thus, daily vinegar ingestion over four weeks improved self-reported depression symptomology in healthy overweight adults, and enhancements in niacin metabolism may factor into this improvement.

Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial.

COVID-19 infection and vaccination offer disparate levels of defense against reinfection and breakthrough infection. This study was designed to examine the effects of curcumin supplementation, specifically HydroCurc (CURC), versus placebo (CON) on circulating inflammatory biomarkers in adults who had previously been diagnosed with COVID-19 and subsequently received a primary series of monovalent vaccine doses. This study was conducted between June 2021 and May 2022. Participants were randomized to receive CURC (500 mg) or CON capsules twice daily for four weeks. Blood sampling was completed at baseline and week-4 and analyzed for biomarkers. Linear regression was utilized to examine the between-group differences in post-trial inflammatory biomarker levels, adjusting for baseline and covariates including age, sex, race/ethnicity, and interval between COVID-19 diagnosis and trial enrollment. The sample (n = 31) was 71% female (Age 27.6 ± 10.4 y). The CURC group exhibited significantly lower post-trial concentrations of proinflammatory IL-6 (ß = -0.52, 95%CI: -1.03, -0.014, p = 0.046) and MCP-1 (ß = -0.12, 95%CI: -0.23, -0.015, p = 0.027) compared to CON, adjusting for baseline and covariates. Curcumin intake confers anti-inflammatory activity and may be a promising prophylactic nutraceutical strategy for COVID-19. These results suggest that 4 weeks of curcumin supplementation resulted in significantly lower concentrations of proinflammatory cytokines in adults who recovered from COVID-19 infection and were subsequently vaccinated.

Erythrocyte osmotic fragility is not linked to vitamin C nutriture in adults with well-controlled type 2 diabetes.

Erythrocyte fragility is amplified by oxidative stress and linked to diabetes-specific microvascular disease. Vitamin C supplementation improves glycemic indices in adults with type 2 diabetes (T2D) by improving antioxidant status. This cross-sectional study examined the relationships between vitamin C status and erythrocyte osmotic fragility in adults with or without T2D. Participants provided a fasting blood sample for erythrocyte osmotic fragility testing as a function of hypotonic NaCl concentrations. Additionally, plasma was stabilized with metaphosphoric acid prior to vitamin C analysis using isocratic reverse-phase UV-HPLC separation. Participants were grouped as diagnosed T2D (n = 14; 36% female; 55.5 ± 8.2 y; 31.5 ± 9.0 kg/m2; HbA1c: 7.4 ± 1.9%; plasma vitamin C: 36.0 ± 12.2 µM) or no diabetes (n = 16; 69% female; 38.7 ± 13.5 y; 26.8 ± 6.6 kg/m2; HbA1c: 5.4 ± 0.3%; plasma vitamin C: 34.8 ± 10.9 µM). Participant characteristics differed between groups only for age and hemoglobin A1c (HbA1c; p < 0.05). All hemolysis parameters were in normal ranges for the participants with T2D, and no significant differences in hemolysis parameters were noted between those with or without T2D. However, among participants with T2D, the NaCl concentration eliciting 50% hemolysis was higher for those with low (<7%) vs. high (>7%) HbA1c values (p = 0.037) indicating a slightly higher erythrocyte fragility in the former group. Vitamin C status did not impact any of the hemolysis parameters in adults with or without T2D. Thus, erythrocyte fragility was not elevated in T2D, and vitamin C nutriture was not related to erythrocyte fragility in adults with well-controlled T2D.

Daily Vinegar Ingestion Improves Depression Scores and Alters the Metabolome in Healthy Adults: A Randomized Controlled Trial.

Daily vinegar ingestion has been linked to improved glycemic control, but recent data suggest a separate unexplored role for vinegar in mental health. Utilizing a placebo-controlled, parallel arm study design, this 4-week trial examined the impact of daily vinegar ingestion on mood states and urinary metabolites in healthy college students. Participants were randomized to the vinegar group (VIN: n = 14; 1.5 g acetic acid/day as liquid vinegar) or the control group (CON: n = 11; 0.015 g acetic acid/day as a pill) with no change to customary diet or physical activity. At baseline and at study week four, participants completed the Profile of Mood States (POMS) and the Center for Epidemiological Studies-Depression (CES-D) questionnaires and provided a first-morning urine sample for targeted metabolomics analyses. The change in both POMS depression scores and CES-D scores differed significantly between groups favoring improved affect in the VIN versus CON participants after four weeks. Metabolomics analyses pre and post-intervention suggested metabolite alterations associated with vinegar ingestion that are consistent for improved mood, including enzymatic dysfunction in the hexosamine pathway as well as significant increases in glycine, serine, and threonine metabolism. These data warrant continued investigation of vinegar as a possible agent to improve mood state.