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Mao W, Liu X, Fan S, Zhang R, Liu M, Xiao S. Modulating oxidative stress: a reliable strategy for coping with community-acquired pneumonia in older adults. Front Med (Lausanne) 2025; 12:1549658. [PMID: 40206465 PMCID: PMC11979195 DOI: 10.3389/fmed.2025.1549658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 03/11/2025] [Indexed: 04/11/2025] Open
Abstract
Community-acquired pneumonia (CAP) remains one of the leading respiratory diseases worldwide. With the aging of the global population, the morbidity, criticality and mortality rates of CAP in older adults remain high every year. Modulating the signaling pathways that cause the inflammatory response and improve the immune function of patients has become the focus of reducing inflammatory damage in the lungs, especially CAP in older adults. As an important factor that causes the inflammatory response of CAP and affects the immune status of the body, oxidative stress plays an important role in the occurrence, development and treatment of CAP. Furthermore, in older adults with CAP, oxidative stress is closely associated with immune senescence, sarcopenia, frailty, aging, multimorbidity, and polypharmacy. Therefore, multiple perspectives combined with the disease characteristics of older adults with CAP were reviewed to clarify the research progress and application value of modulating oxidative stress in older adults with CAP. Clearly, there is no doubt that targeted modulation of oxidative stress benefits CAP in older adults. However, many challenges and unknowns concerning how to modulate oxidative stress for further practical clinical applications exist, and more targeted research is needed. Moreover, the limitations and challenges of modulating oxidative stress are analyzed with the aim of providing references and ideas for future clinical treatment or further research in older adults with CAP.
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Affiliation(s)
- Weixu Mao
- Department of Respiratory Medicine, The Affiliated Yongchuan Traditional Chinese Medicine Hospital of Chongqing Medical University, Chongqing, China
| | - Xuanjun Liu
- Department of General Surgery, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Senji Fan
- Department of Respiratory Medicine, The Affiliated Yongchuan Traditional Chinese Medicine Hospital of Chongqing Medical University, Chongqing, China
| | - Ruibin Zhang
- Department of Respiratory Medicine, The Affiliated Yongchuan Traditional Chinese Medicine Hospital of Chongqing Medical University, Chongqing, China
| | - Miao Liu
- Department of Respiratory Medicine, The Affiliated Yongchuan Traditional Chinese Medicine Hospital of Chongqing Medical University, Chongqing, China
| | - Shunqiong Xiao
- Department of Respiratory Medicine, The Affiliated Yongchuan Traditional Chinese Medicine Hospital of Chongqing Medical University, Chongqing, China
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Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Knutsen HK, Maciuk A, Mangelsdorf I, McArdle HJ, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Traber MG, Vrolijk M, Bercovici CM, de Sesmaisons Lecarré A, Fabiani L, Karavasiloglou N, Mendes V, Valtueña Martínez S, Naska A. Scientific opinion on the tolerable upper intake level for vitamin E. EFSA J 2024; 22:e8953. [PMID: 39099617 PMCID: PMC11294871 DOI: 10.2903/j.efsa.2024.8953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/06/2024] Open
Abstract
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As α-tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to α-tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer. The effect on blood clotting and associated increased risk of bleeding is considered as the critical effect to establish an UL for vitamin E. No new evidence has been published that could improve the characterisation of a dose-response. The ULs for vitamin E from all dietary sources, which were previously established by the Scientific Committee on Food, are retained for all population groups, i.e. 300 mg/day for adults, including pregnant and lactating women, 100 mg/day for children aged 1-3 years, 120 mg/day for 4-6 years, 160 mg/day for 7-10 years, 220 mg/day for 11-14 years and 260 mg/day for 15-17 years. A UL of 50 mg/day is established for infants aged 4-6 months and a UL of 60 mg/day for infants aged 7-11 months. ULs apply to all stereoisomeric forms of α-tocopherol. ULs do not apply to individuals receiving anticoagulant or antiplatelet medications (e.g. aspirin), to patients on secondary prevention for CVD or to patients with vitamin K malabsorption syndromes. It is unlikely that the ULs for vitamin E are exceeded in European populations, except for regular users of food supplements containing high doses of vitamin E.
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de Jesus RP, de Carvalho JF, de Oliveira LPM, Cunha CDM, Alves TCHS, Vieira STB, Figueiredo VM, Bueno AA. Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2. World J Hepatol 2022; 14:80-97. [PMID: 35126841 PMCID: PMC8790394 DOI: 10.4254/wjh.v14.i1.80] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/28/2021] [Accepted: 12/22/2022] [Indexed: 02/06/2023] Open
Abstract
Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients.
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Affiliation(s)
- Rosangela Passos de Jesus
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | | | | | - Carla de Magalhães Cunha
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Thaisy Cristina Honorato Santos Alves
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Sandra Tavares Brito Vieira
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Virginia Maria Figueiredo
- Department of Gastroenterology, IPEMED, Ipemed Faculty of Medical Sciences, Salvador 40170-110, Bahia, Brazil
| | - Allain Amador Bueno
- College of Health, Life and Environmental Sciences, University of Worcester, Worcester WR2 6AJ, United Kingdom
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Wagener BM, Anjum N, Evans C, Brandon A, Honavar J, Creighton J, Traber MG, Stuart RL, Stevens T, Pittet JF. α-Tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia. Am J Respir Cell Mol Biol 2020; 63:234-243. [PMID: 32243761 DOI: 10.1165/rcmb.2019-0185oc] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen, including increased lung permeability in a Toll-like receptor 4/RhoA/PAI-1 (plasminogen activator inhibitor-1)-dependent manner. α-Tocopherol has antiinflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, RhoA and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (ExoY) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation, and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic resistant. We provide evidence that α-tocopherol could be a useful therapeutic agent for individuals who are susceptible to infection with P. aeruginosa, such as those who are immunocompromised or critically ill.
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Affiliation(s)
- Brant M Wagener
- Department of Anesthesiology and Perioperative Medicine.,Center for Free Radical Biology, and
| | - Naseem Anjum
- Department of Anesthesiology and Perioperative Medicine
| | - Cilina Evans
- Department of Anesthesiology and Perioperative Medicine
| | | | | | | | - Maret G Traber
- Linus Pauling Institute, Oregon State University, Corvallis, Oregon
| | | | - Troy Stevens
- Department of Pharmacology and Medicine and the Center for Lung Biology, University of South Alabama, Mobile, Alabama
| | - Jean-Francois Pittet
- Department of Anesthesiology and Perioperative Medicine.,Center for Lung Injury and Repair, University of Alabama at Birmingham, Birmingham, Alabama
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Hemilä H. Vitamin E and Mortality in Male Smokers of the ATBC Study: Implications for Nutritional Recommendations. Front Nutr 2020; 7:36. [PMID: 32296711 PMCID: PMC7136753 DOI: 10.3389/fnut.2020.00036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/09/2020] [Indexed: 12/30/2022] Open
Abstract
The Dietary Reference Intakes (DRI)-monograph (USA/Canada) states that the estimated average requirement (EAR) of vitamin E for men and women of any age is 12 mg/day. The EAR value is based on in vitro hemolysis in young males; a surrogate endpoint without any direct validity. The EAR is then extrapolated to females and older males. The validity of the EAR level is therefore questionable. Total mortality is an outcome of direct clinical relevance. Investigating the effect of long-term dietary vitamin E intake level on mortality in a randomized trial is, however, not feasible. Nevertheless, the effect of dietary vitamin E intake can be investigated indirectly from the effects of a fixed-level vitamin E supplement administered to participants on variable levels of dietary vitamin E intake. If vitamin E intake below the EAR is harmful, then vitamin E supplement should be beneficial to those people who have dietary vitamin E intake level below the EAR. The purpose of this study was to analyze the association between dietary vitamin E intake and the effect of 25 mg/day of vitamin E supplement on total mortality in Finnish male smokers aged 50-69 years in the Alpha-Tocopherol-Beta-Carotene (ATBC) Study. The effect of vitamin E supplement was estimated by Cox regression. Among participants who had dietary vitamin C intake of 90 mg/day and above, vitamin E supplement increased mortality by 19% (p = 0.006) in those aged 50-62 years, but decreased mortality by 41% (p = 0.0003) in those aged 66-69 years. No association between vitamin E supplement effect and dietary vitamin E intake was found in these two groups, nor in participants who had dietary vitamin C intake less than 90 mg/day. There is no evidence in any of the analyzed subgroups that there is a difference in the effect of the 25 mg/day vitamin E supplement on males on dietary vitamin E intakes below vs. above the EAR of 12 mg/day. This analysis of the ATBC Study found no support for the 'estimated average requirement' level of 12 mg/day of vitamin E for older males. Trial registration: ClinicalTrials.gov, identifier: NCT00342992.
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Affiliation(s)
- Harri Hemilä
- Department of Public Health, University of Helsinki, Helsinki, Finland
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The effect of β-carotene on the mortality of male smokers is modified by smoking and by vitamins C and E: evidence against a uniform effect of nutrient. J Nutr Sci 2020; 9:e11. [PMID: 32215208 PMCID: PMC7082716 DOI: 10.1017/jns.2020.3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found that β-carotene supplementation increased the risk of pneumonia 4-fold in those who started smoking at the age of ≥21 years and smoked ≥21 cigarettes/d (a subgroup of 7 % of the study population). The present study hypothesised that β-carotene increases mortality in the same subgroup. The ATBC Study (1985–1993) recruited 29 133 Finnish male smokers (≥5 cigarettes/d) aged 50–69 years. Cox regression models were constructed to estimate the effect of β-carotene supplementation in subgroups. β-Carotene increased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at ≥21 years and smoked ≥21 cigarettes/d. Within this subgroup, there was strong evidence of further heterogeneity. The effect of β-carotene supplementation was further modified by dietary vitamin C intake, fruit and vegetable intake (P = 0·0004), and by vitamin E supplementation (P = 0·011). Thus, harm from β-carotene was not uniform within the study population. Interactions between β-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not be extrapolated to the general population. Heterogeneity of the β-carotene effect on mortality challenges the validity of previous meta-analyses that have pooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants and all people. Trial registration: ClinicalTrials.gov NCT00342992.
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Hemilä H. Effect of β-Carotene Supplementation on the Risk of Pneumonia Is Heterogeneous in Males: Effect Modification by Cigarette Smoking. J Nutr Sci Vitaminol (Tokyo) 2019; 64:374-378. [PMID: 30381628 DOI: 10.3177/jnsv.64.374] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Beta-carotene has been suggested to be a factor for improving the immune system, which implies that it might decrease the risk of infections. We therefore analyzed whether beta-carotene supplementation influenced pneumonia risk in 14,564 Finnish male smokers of the Alpha-Tocopherol Beta-Carotene (ATBC) Study. There were 231 pneumonia cases in the beta-carotene group and 217 cases in the placebo group. Thus, beta-carotene had no effect on the average incidence of pneumonia, RR=1.07 (95% CI: 0.89-1.29). However, cigarette smoking exposure significantly modified the effect. Beta-carotene increased pneumonia risk by RR=4.0 (95% CI: 1.63-10) among 990 participants who started to smoke at the age of ≥21 y and smoked ≥21 cigarettes per day at the study baseline. However, beta-carotene had no influence on pneumonia risk for the remaining participants. We also analyzed the effect of beta-carotene on participants who quit smoking during the ATBC Study. Among 4,290 participants who quit smoking, the 58 pneumonia cases were evenly distributed between the beta-carotene and placebo groups with RR=0.93 (95% CI: 0.55-1.55). Accordingly, no evidence was found that beta-carotene decreased pneumonia risk; instead, it significantly increased the incidence of pneumonia in a subgroup that covered 7% of the study population.
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Affiliation(s)
- Harri Hemilä
- Department of Public Health, University of Helsinki
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Hemilä H. Letter: Comparison of different vitamin E forms is confounded by heterogeneity in vitamin E effects. Nutr Rev 2018; 76:722-723. [PMID: 30010872 DOI: 10.1093/nutrit/nuy038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Harri Hemilä
- Department of Public Health, University of Helsinki, Tukholmankatu 8 B, Helsinki, Finland
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Abstract
In the early literature, vitamin C deficiency was associated with pneumonia. After its identification, a number of studies investigated the effects of vitamin C on diverse infections. A total of 148 animal studies indicated that vitamin C may alleviate or prevent infections caused by bacteria, viruses, and protozoa. The most extensively studied human infection is the common cold. Vitamin C administration does not decrease the average incidence of colds in the general population, yet it halved the number of colds in physically active people. Regularly administered vitamin C has shortened the duration of colds, indicating a biological effect. However, the role of vitamin C in common cold treatment is unclear. Two controlled trials found a statistically significant dose-response, for the duration of common cold symptoms, with up to 6-8 g/day of vitamin C. Thus, the negative findings of some therapeutic common cold studies might be explained by the low doses of 3-4 g/day of vitamin C. Three controlled trials found that vitamin C prevented pneumonia. Two controlled trials found a treatment benefit of vitamin C for pneumonia patients. One controlled trial reported treatment benefits for tetanus patients. The effects of vitamin C against infections should be investigated further.
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Affiliation(s)
- Harri Hemilä
- Department of Public Health, University of Helsinki, Helsinki FI-00014, Finland.
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Hemilä H. Vitamin E administration may decrease the incidence of pneumonia in elderly males. Clin Interv Aging 2016; 11:1379-1385. [PMID: 27757026 PMCID: PMC5055121 DOI: 10.2147/cia.s114515] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Vitamin E has influenced the immune system in laboratory studies. Dozens of animal experiments have found that vitamin E offered protection against infections caused by viruses and bacteria. Previously, significant heterogeneity was found in the effect of vitamin E supplementation on pneumonia in humans. The aim of this study was to examine how the effect of vitamin E on pneumonia risk depends on age. Methods Secondary analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study in Finland, 1985–1993, was performed. Participants were male smokers aged 50–69 years at the baseline who started to smoke at ≥21 years (N=7,469). Intervention was 50 mg/d of vitamin E for 5–8 years. The outcome was the incidence of hospital-treated, community-acquired pneumonia by the age at the follow-up. Results Among 2,216 participants who smoked 5–19 cigarettes per day at baseline and exercised at leisure time, vitamin E supplementation reduced the incidence of pneumonia by 69% (95% confidence interval [CI]: 43%–83%; 57 pneumonia cases). In this subgroup, vitamin E prevented pneumonia in 12.9% of participants by the age of 74 years. Among 5,253 participants who smoked ≥20 cigarettes per day at baseline or did not exercise, the incidence of pneumonia was 14% lower in the vitamin E participants (95% CI: −38% to +21%; 139 cases). One-third of the participants quit smoking for a period, of whom 27 got pneumonia. The incidence of pneumonia was 72% (95% CI: 31%–89%) lower in the vitamin E group, and this benefit was also seen among those males who smoked ≥20 cigarettes per day at baseline or did not exercise. Conclusion Although the evidence of benefit from vitamin E against pneumonia in elderly males is strong in this analysis, the overall findings about vitamin E have been complex. Further research on vitamin E in nonsmoking elderly males is warranted.
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Affiliation(s)
- Harri Hemilä
- Department of Public Health, University of Helsinki, Helsinki, Finland
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