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Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Rasa, S, Nora-Krukle, Z, Henning, N, Eliassen, E, Shikova, E, Harrer, T, Scheibenbogen, C, Murovska, M, Prusty, BK
Journal of translational medicine. 2018;16(1):268
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The causes of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are currently unknown, however viruses have been implicated. The absence of well-designed studies has hindered the understanding of this disease and the aim of this review was to discuss the literature regarding viruses and ME/CFS. Several viruses were discussed including the herpes virus, which is responsible for illnesses such as chicken pox and cold sores. This virus has not always been associated with the onset of ME/CFS, however it may be in certain individuals. The enteroviruses, which are responsible for illnesses such as hand, foot and mouth and polio, were also reviewed and it was concluded that it is unlikely that these have a role in ME/CFS. Several other viruses were also discussed. The authors then went on to describe how these viruses can affect human cells, potentially causing ME/CFS. It was concluded that the data available is controversial and only certain individuals may be affected, better studies are required. This study could be used by healthcare professionals to identify individuals at risk of ME/CFS following viral infection and understanding how ME/CFS may develop.
Abstract
BACKGROUND AND MAIN TEXT Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. CONCLUSIONS This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease.
Soliman, GA
Nutrients. 2018;10(6)
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For years, dietary cholesterol was implicated in increasing blood cholesterol levels, therefore contributing to the development of cardiovascular disease (CVD). While it is known that saturated fatty acids and trans-fatty acids increase CVD risk, the evidence of dietary cholesterol increasing this risk remains inconclusive. This review summarises the current evidence regarding dietary cholesterol, blood cholesterol, saturated fatty acids and the risk of CVD. This review found that the current literature does not support the notion that dietary cholesterol increases the risk of heart disease in healthy individuals. The fact that dietary cholesterol is common in foods that are high in saturated fats may have contributed to the hypothesis that dietary cholesterol increases the risk of CVD. Based on these results, the author suggests individuals incorporate nutrient-dense, calorie controlled, balanced meals in eating patterns.
Abstract
Cardiovascular disease (CVD) is the leading cause of death in the United States. For years, dietary cholesterol was implicated in increasing blood cholesterol levels leading to the elevated risk of CVD. To date, extensive research did not show evidence to support a role of dietary cholesterol in the development of CVD. As a result, the 2015⁻2020 Dietary Guidelines for Americans removed the recommendations of restricting dietary cholesterol to 300 mg/day. This review summarizes the current literature regarding dietary cholesterol intake and CVD. It is worth noting that most foods that are rich in cholesterol are also high in saturated fatty acids and thus may increase the risk of CVD due to the saturated fatty acid content. The exceptions are eggs and shrimp. Considering that eggs are affordable and nutrient-dense food items, containing high-quality protein with minimal saturated fatty acids (1.56 gm/egg) and are rich in several micronutrients including vitamins and minerals, it would be worthwhile to include eggs in moderation as a part of a healthy eating pattern. This recommendation is particularly relevant when individual’s intakes of nutrients are suboptimal, or with limited income and food access, and to help ensure dietary intake of sufficient nutrients in growing children and older adults.
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Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.
Pagliari, D, Saviano, A, Newton, EE, Serricchio, ML, Dal Lago, AA, Gasbarrini, A, Cianci, R
Mediators of inflammation. 2018;2018:7946431
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Gut microbiota homeostasis plays a central role in modulating the mucosal immune system. Increasing research has shown a correlation between an imbalanced gut microbiota, called dysbiosis, and various pancreatic disorders. The aim of this review was to analyse current data linking the gut microbiome and several pancreatic disorders. The current evidence demonstrates gut dysbiosis is correlated with the duration and prognosis of pancreatic disorders. While this may lead to early detection of several pancreatic disorders, it remains unclear whether dysbiosis is a cause or effect of pancreatic disorders. Based on these results, the authors conclude future studies are required to better understand the crosstalk between gut microbiota and the immune system to improve diagnostic and treatment strategies for pancreatic disorders.
Abstract
Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.
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Potential of Mushroom Compounds as Immunomodulators in Cancer Immunotherapy: A Review.
Ayeka, PA
Evidence-based complementary and alternative medicine : eCAM. 2018;2018:7271509
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Edible mushrooms strengthen the immune system and are considered biological response modifiers (BRMs). This article reviews the research behind the use of mushroom compounds in cancer therapy. Beta-glucans from the cell walls of mushrooms are the major polysaccharide fraction that is responsible for immune modulating effects, through a number of mechanisms which are explored in this review article. Other important components include other polysaccharides, polysaccharide-protein complexes, agaritine, ergosterol, selenium, polyphenols, and terpenoids. Anti-cancer effects are mediated by stimulating lymphocytes, NK cells, and macrophages (all three specific immune cells), enhancing production of cytokines (immune messengers), inhibiting proliferation of cancer cells, promoting apoptosis (programmed cell death), and blocking angiogenesis (the development of blood vessels that feed the tumour), in addition to being cytotoxic to cancer cells. Medicinal mushrooms from which these compounds are derived and which have been researched for the treatment of various cancers include Ganoderma lucidum, G. tsugae, Schizophyllum commune, Sparassis crispa, Pleurotus tuberregium, P. rhinoceros, Trametes robiniophila Murill, Coriolus versicolor, Lentinus edodes, Grifola frondosa, and Flammulina velutipes, among others. Cancers in which benefits from medicinal mushrooms have been reported include breast, colorectal, cervical, skin, liver, ovarian, bladder, prostate, gastric, skin, lung, leukaemia, and stomach cancers.
Abstract
Since time immemorial, plants and their compounds have been used in the treatment and management of various ailments. Currently, most of conventional drugs used for treatment of diseases are either directly or indirectly obtained from plant sources. The fungal group of plants is of significance, which not only provides food directly to man but also has been source of important drugs. For instance, commonly used antibiotics are derived from fungi. Fungi have also been utilized in the food industry, baking, and alcohol production. Apart from the economic importance of the microfungi, macrofungi have been utilized directly as food, which is usually got from their fruiting bodies, commonly known as mushrooms. Due to their richness in proteins, minerals, and other nutrients, mushrooms have also been associated with boosting the immune system. This makes mushrooms an important food source, especially for vegetarians and immunosuppressed individuals including the HIV/AIDS persons. In complementary and alternative medicines (CAMs), mushrooms are increasingly being accepted for treatment of various diseases. Mushrooms have been shown to have the ability to stimulate the immune system, modulate humoral and cellular immunity, and potentiate antimutagenic and antitumorigenic activity, as well as rejuvenating the immune system weakened by radiotherapy and chemotherapy in cancer treatment. This potential of mushrooms, therefore, qualifies them as candidates for immunomodulation and immunotherapy in cancer and other diseases' treatment. However, a critical review on mushroom's immune modulating potential in cancer has not been sufficiently addressed. This review puts forward insights into the immune activities of mushroom associated with anticancer activities.
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Inflammaging and the Lung.
Kovacs, EJ, Boe, DM, Boule, LA, Curtis, BJ
Clinics in geriatric medicine. 2017;33(4):459-471
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Characteristic of ageing is the presence of inflammatory markers in the blood and lead to the term inflammageing being coined. Inflammatory markers may contribute to chronic disease such as diseases of the lung. This review of 122 papers aimed to address the role of inflammageing on the lungs. The paper discussed the changes that the lungs immune cells go through with ageing and the impairment that they experience, with inflammageing playing a role. Causes of inflammageing were discussed and gut permeability, the halting of cell division and the stimulation of larger molecules in the body to release inflammatory markers were all implicated. Gut permeability which is a newer area of research with regards to inflammageing, was extensively discussed and allows more bacteria and pathogens into the body causing an inflammatory reaction. It was concluded that reducing inflammageing is a target for treatments in the elderly, whether these directly target inflammation or the underlying cause, requires more research. This paper could be used by healthcare professionals as a basis to understand inflammageing and where it may be appropriate to target inflammation in the elderly.
Abstract
With the coming of the "silver tsunami," expanding the knowledge about how various intrinsic and extrinsic factors affect the immune system in the elderly is timely and of immediate clinical need. The global population is increasing in age. By the year 2030, more than 20% of the population of the United States will be older than 65 years of age. This article focuses on how advanced age alters the immune systems and how this, in turn, modulates the ability of the aging lung to deal with infectious challenges from the outside world and from within the host.
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Probiotics for the Treatment of Atopic Dermatitis in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Huang, R, Ning, H, Shen, M, Li, J, Zhang, J, Chen, X
Frontiers in cellular and infection microbiology. 2017;7:392
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It is estimated that atopic dermatitis (AD) affects around 10-20% of children. This systematic review and meta-analysis evaluates the evidence for using probiotics for the treatment of AD in children. 13 randomised controlled trials (RCT) were included in the review, all but one were of a double-blind design. They included a total of 1070 children, 553 receiving probiotics and 517 controls. Overall, a beneficial effect of probiotics in AD was observed. Subgroup analysis showed a) positive results in children aged 1-18 years, but probiotics being ineffective in infants younger than 1 year; b) probiotics reduced AD in Asian, but not European studies, and c) certain strains proved beneficial (Lactobacillus salivarius, Lactobacillus fermentum and a multi-strain probiotic), whilst Lactobacillus rhamnosus GG and Lactobacillus plantarum showed no effect. The authors discuss that their meta-analysis is limited by the heterogeneity among the trials and inclusion of studies with small sample sizes. They conclude that probiotics may be of benefit in children with AD but that more adequately powered trials assessing specific probiotics and dosages are needed, to inform the best treatment protocols.
Abstract
Objective: Atopic dermatitis (AD) is a prevalent, burdensome, and psychologically important pediatric concern. Probiotics have been suggested as a treatment for AD. Some reports have explored this topic; however, the utility of probiotics for AD remains to be firmly established. Methods: To assess the effects of probiotics on AD in children, the PubMed/Medline, Cochrane Library Scopus, and OVID databases were searched for reports published in the English language. Results: Thirteen studies were identified. Significantly higher SCORAD values favoring probiotics over controls were observed (mean difference [MD], -3.07; 95% confidence interval [CI], -6.12 to -0.03; P < 0.001). The reported efficacy of probiotics in children < 1 year old was -1.03 (95%CI, -7.05 to 4.99) and that in children 1-18 years old was -4.50 (95%CI, -7.45 to -1.54; P < 0.001). Subgroup analyses showed that in Europe, SCORAD revealed no effect of probiotics, whereas significantly lower SCORAD values were reported in Asia (MD, -5.39; 95%CI, -8.91 to -1.87). Lactobacillus rhamnosus GG (MD, 3.29; 95%CI, -0.30 to 6.88; P = 0.07) and Lactobacillus plantarum (MD, -0.70; 95%CI, -2.30 to 0.90; P = 0.39) showed no significant effect on SCORAD values in children with AD. However, Lactobacillus fermentum (MD, -11.42; 95%CI, -13.81 to -9.04), Lactobacillus salivarius (MD, -7.21; 95%CI, -9.63 to -4.78), and a mixture of different strains (MD, -3.52; 95%CI, -5.61 to -1.44) showed significant effects on SCORAD values in children with AD. Conclusions: Our meta-analysis indicated that the research to date has not robustly shown that probiotics are beneficial for children with AD. However, caution is needed when generalizing our results, as the populations evaluated were heterogeneous. Randomized controlled trials with larger samples and greater power are necessary to identify the species, dose, and treatment duration of probiotics that are most efficacious for treating AD in children.
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The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis.
Miller, LE, Lehtoranta, L, Lehtinen, MJ
Nutrients. 2017;9(3)
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Elderly individuals are more susceptible to infections and cancer, due to lowered immune system function. The gut bacteria play a key role in human immune system function and there is an interest in a potential role for probiotics in strengthening the immune system through manipulation of the microbiome. This systematic review and meta-analysis of 4 randomised controlled trials aimed to examine the efficacy of Bifidobacterium animalis lactis HN019 on the cellular immune activity of healthy elderly adults age 60-70 years. The authors concluded that supplementation with this bacterial strain at a range of potencies for 3-6 weeks duration had a significant positive impact on the part of the immune system that is responsible for removing pathogens and cell debris (phagocytosis) and a lesser but nevertheless significant impact on natural killer cells responsible for tumour destruction.
Abstract
Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function. The objective of this work was to determine the efficacy of Bifidobacterium (B.) animalis ssp. lactis HN019 (HN019) supplementation on cellular immune activity in healthy elderly subjects. We conducted a systematic review of Medline and Embase for controlled trials that reported polymorphonuclear (PMN) cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following B. lactis HN019 consumption in the elderly. A random effects meta-analysis was performed with standardized mean difference (SMD) and 95% confidence interval between probiotic and control groups for each outcome. A total of four clinical trials were included in this analysis. B. lactis HN019 supplementation was highly efficacious in increasing PMN phagocytic capacity with an SMD of 0.74 (95% confidence interval: 0.38 to 1.11, p < 0.001) and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% confidence interval: 0.08 to 0.78, p = 0.02). The main limitations of this research were the small number of included studies, short-term follow-up, and assessment of a single probiotic strain. In conclusion, daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults.
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A novel boswellic acids delivery form (Casperome®) in the management of musculoskeletal disorders: a review.
Riva, A, Allegrini, P, Franceschi, F, Togni, S, Giacomelli, L, Eggenhoffner, R
European review for medical and pharmacological sciences. 2017;21(22):5258-5263
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Musculoskeletal conditions, including osteoarthritis, inflammatory arthritis, musculoskeletal injuries, gout and metabolic bone disease, are the most common cause of chronic disability worldwide. Treatment with analgesic and/or anti-inflammatory medication carries a significant risk of side effects. Botanical extracts are also commonly used for the management of musculoskeletal disorders, and in addition to having less side effects they may have a beneficial effect on the course of the disease. This review focuses on the use of boswellic acids (BA, from Frankincense, Boswellia serrata and Boswellia carterii) in the treatment of musculoskeletal conditions. In pre-clinical experiments, BAs have been shown to be anti-inflammatory and improve antioxidant status. In several clinical trials BSE was superior to placebo in reducing pain and increasing functionality in osteoarthritis. BSE are poorly absorbed, and both clinical and pre-clinical research has shown that a combination of BAs with lecithin (Casperome®) enhances absorption and bioavailability. Casperome® has been investigated in a number of clinical trials and has been shown to be of benefit in tendinopathies (inflammation of the elbow and Achilles tendon), radiculopathies (pinched nerves), sprained ankles and sports injuries. The authors conclude that Casperome® is a promising remedy as part of an integrated approach to musculoskeletal disorders.
Abstract
Standard pharmacological treatment of musculoskeletal conditions is often associated with relevant side effects. Botanical preparations endowed with a good tolerability profile, therefore, could have a role in the management of these disorders. Among different natural products, Boswellia serrata extracts have long been used for the treatment of musculoskeletal disorders, given their marked anti-inflammatory activity and their ability to promote tissue regeneration. However, standard preparations of Boswellia serrata show overall modest pharmacokinetic properties, a limitation which may ultimately lead to reduced efficacy. In an effort to improve the pharmacokinetic properties, Casperome®, a lecithin-based formulation of Boswellia serrata extract representing the whole natural bouquet, has been developed. This formulation was effective in the treatment of Achilles tendonitis, epicondylitis, radiculopathies, ankle sprains and sport injuries as shown in several clinical studies, the majority of which with a randomized design and all evaluating a number of well-recognized parameters of efficacy for the therapy of musculoskeletal disorder. All studies were consistent in showing a prompt decrease of pain and improvement of functionality of the affected area after supplementation with Casperome®, without any relevant adverse effect. Remarkably, these symptomatic improvements were paralleled by reduced plasmatic levels of inflammatory markers and by a diminished need for rescue analgesics. On these bases, Casperome® may have a role in the treatment of musculoskeletal disorders. Clinical studies in other similar conditions (e.g., osteoarthritis) appear warranted to further investigate the efficacy of this botanical product in more specific settings.
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Vitamin C and Infections.
Hemilä, H
Nutrients. 2017;9(4)
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This article reviews the available literature on the effect of vitamin C on infections. In the early 20th century scurvy was found to be due to vitamin C deficiency and it was also observed that lack of vitamin C predisposed to infections, in particular pneumonia, which sparked interest in the connection between vitamin C and infections. Infections increase oxidative stress which may lead to a decrease in plasma levels of vitamin C, which has antioxidant properties, and much higher intakes of vitamin C may be necessary to maintain sufficiently high plasma levels during an infection. In animal studies vitamin C has been found to be beneficial against various infectious agents including bacteria, viruses, Candida albicans, and protozoa. The common cold is the most widely studied infection with regards to vitamin C. Vitamin C supplementation has been shown to only decrease the incidence of the common cold in specific subgroups but not the population as a whole. However, supplementing no less than 1g vitamin C per day significantly shortened the duration and alleviated severity of colds. Interpretation of studies is complicated by a number of factors, including dose of vitamin C, with up to a 240-fold difference between the lowest and highest vitamin C supplementary dose used in the common cold trials. This review also discusses why interest in the vitamin C/common cold research plummeted in the mid-1970s. Studies on vitamin C and pneumonia showed benefits, but as all these trials were done in specific population groups, the results cannot necessarily be generalised. There is insufficient clinical research into the use of vitamin C for other infections. The author concludes that in view of vitamin C being safe and cheap even modest clinical effects are worth exploring.
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.